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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Discovery of ML366, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="Probe Reports from the NIH Molecular Libraries Program [Internet]">
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<meta name="citation_title" content="Discovery of ML366, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator">
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<meta name="citation_publisher" content="National Center for Biotechnology Information (US)">
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<meta name="citation_date" content="2014/09/18">
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<meta name="citation_author" content="Patrick Faloon">
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<meta name="citation_author" content="Ivan Jewett">
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<meta name="citation_author" content="Willmen Youngsaye">
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<meta name="citation_author" content="Melissa Bennion">
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<meta name="citation_author" content="Wai-Leung Ng">
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<meta name="citation_author" content="Amanda Hurley">
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<meta name="citation_author" content="Timothy A. Lewis">
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<meta name="citation_author" content="Rahul V. Edwankar">
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<meta name="citation_author" content="Hanh Le">
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<meta name="citation_author" content="Carrie M. Mosher">
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<meta name="citation_author" content="Stephen Johnston">
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<meta name="citation_author" content="Sivaraman Dandapani">
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<meta name="citation_author" content="Benito Munoz">
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<meta name="citation_author" content="Michelle Palmer">
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<meta name="citation_author" content="Bonnie L. Bassler">
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<meta name="citation_author" content="Stuart L. Schreiber">
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<meta name="citation_pmid" content="24624463">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK189922/">
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<meta name="DC.Title" content="Discovery of ML366, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator">
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<meta name="DC.Contributor" content="Patrick Faloon">
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<meta name="DC.Contributor" content="Ivan Jewett">
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<meta name="DC.Contributor" content="Willmen Youngsaye">
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<meta name="DC.Contributor" content="Melissa Bennion">
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<meta name="DC.Contributor" content="Wai-Leung Ng">
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<meta name="DC.Contributor" content="Amanda Hurley">
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<meta name="DC.Contributor" content="Timothy A. Lewis">
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<meta name="DC.Contributor" content="Rahul V. Edwankar">
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<meta name="DC.Contributor" content="Hanh Le">
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<meta name="DC.Contributor" content="Carrie M. Mosher">
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<meta name="DC.Contributor" content="Stephen Johnston">
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<meta name="DC.Contributor" content="Sivaraman Dandapani">
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<meta name="DC.Contributor" content="Benito Munoz">
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<meta name="DC.Contributor" content="Michelle Palmer">
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<meta name="DC.Contributor" content="Bonnie L. Bassler">
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<meta name="DC.Contributor" content="Stuart L. Schreiber">
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<meta name="DC.Date" content="2014/09/18">
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<meta name="description" content="Quorum sensing (QS) is a process of bacterial cell-to-cell communication that relies upon recognition of extracellular signaling molecules called autoinducers. QS allows bacteria to synchronize their behavior in response to changes in the population density and species composition of the proximal bacterial community. Known behaviors regulated by QS include bioluminescence, sporulation, virulence factor production, and biofilm formation. We carried out a high throughput screen (HTS) to identify small molecules that modulate QS in a modified V. cholerae strain carrying a luciferase operon; activation of the quorum pathway is accompanied by light production. 352,083 compounds from the National Institutes of Health Molecular Libraries Probe Production Centers Network (NIH-MLPCN) compound library were evaluated. Potential QS modulators were characterized via additional bacterial epistatic assays to elucidate the mode of action. We report the discovery and development of a substituted 2-amino-oxadiazole (ML366) as an inhibitor of Vibrio cholerae LuxO, a response regulator and intracellular kinase. ML366 acts directly on LuxO by inhibiting ATPase activity. ML366 should greatly expand the general understanding of how QS response regulators relay information from upstream signals that lead to modified gene expression. In addition, these compounds could lead to the development of antibacterial drugs designed to interfere with QS which could have enormous ramifications for improving human health.">
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<meta name="og:title" content="Discovery of ML366, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator">
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<meta name="og:description" content="Quorum sensing (QS) is a process of bacterial cell-to-cell communication that relies upon recognition of extracellular signaling molecules called autoinducers. QS allows bacteria to synchronize their behavior in response to changes in the population density and species composition of the proximal bacterial community. Known behaviors regulated by QS include bioluminescence, sporulation, virulence factor production, and biofilm formation. We carried out a high throughput screen (HTS) to identify small molecules that modulate QS in a modified V. cholerae strain carrying a luciferase operon; activation of the quorum pathway is accompanied by light production. 352,083 compounds from the National Institutes of Health Molecular Libraries Probe Production Centers Network (NIH-MLPCN) compound library were evaluated. Potential QS modulators were characterized via additional bacterial epistatic assays to elucidate the mode of action. We report the discovery and development of a substituted 2-amino-oxadiazole (ML366) as an inhibitor of Vibrio cholerae LuxO, a response regulator and intracellular kinase. ML366 acts directly on LuxO by inhibiting ATPase activity. ML366 should greatly expand the general understanding of how QS response regulators relay information from upstream signals that lead to modified gene expression. In addition, these compounds could lead to the development of antibacterial drugs designed to interfere with QS which could have enormous ramifications for improving human health.">
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id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK189922_"><span class="title" itemprop="name">Discovery of ML366, an inhibitor of <i>Vibrio cholerae</i> Quorum Sensing Acting <i>via</i> the LuxO response regulator</span></h1><p class="contribs">Faloon P, Jewett I, Youngsaye W, et al.</p><p class="fm-aai"><a href="#_NBK189922_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p>Quorum sensing (QS) is a process of bacterial cell-to-cell communication that relies upon recognition of extracellular signaling molecules called autoinducers. QS allows bacteria to synchronize their behavior in response to changes in the population density and species composition of the proximal bacterial community. Known behaviors regulated by QS include bioluminescence, sporulation, virulence factor production, and biofilm formation. We carried out a high throughput screen (HTS) to identify small molecules that modulate QS in a modified <i>V. cholerae</i> strain carrying a luciferase operon; activation of the quorum pathway is accompanied by light production. 352,083 compounds from the National Institutes of Health Molecular Libraries Probe Production Centers Network (NIH-MLPCN) compound library were evaluated. Potential QS modulators were characterized <i>via</i> additional bacterial epistatic assays to elucidate the mode of action. We report the discovery and development of a substituted 2-amino-oxadiazole (<a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>) as an inhibitor of <i>Vibrio cholerae</i> LuxO, a response regulator and intracellular kinase. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> acts directly on LuxO by inhibiting ATPase activity. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> should greatly expand the general understanding of how QS response regulators relay information from upstream signals that lead to modified gene expression. In addition, these compounds could lead to the development of antibacterial drugs designed to interfere with QS which could have enormous ramifications for improving human health.</p></div><div class="h2"></div><p><b>Assigned Assay Grant No:</b> R03 MH094166-01</p><p><b>Screening Center Name & PI:</b> Broad institute Probe Development Center, Stuart L. Schreiber, PhD</p><p><b>Chemistry Center Name & PI:</b> Broad institute Probe Development Center, Stuart L. Schreiber, PhD</p><p><b>Assay Submitter & Institution:</b> Bonnie L. Bassler, PhD., Princeton University, Princeton, NJ</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588521" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">588521</a></p><div id="ml366.s1"><h2 id="_ml366_s1_">Probe Structure & Characteristics</h2><div id="ml366.f1" class="figure"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20ml366f1&p=BOOKS&id=189922_ml366f1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f1.jpg" alt="Image ml366f1" class="tileshop" title="Click on image to zoom" /></a></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t1"><a href="/books/NBK189922/table/ml366.t1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml366t1" rid-ob="figobml366t1"><img class="small-thumb" src="/books/NBK189922/table/ml366.t1/?report=thumb" src-large="/books/NBK189922/table/ml366.t1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml366.t1"><a href="/books/NBK189922/table/ml366.t1/?report=objectonly" target="object" rid-ob="figobml366t1">Table</a></h4></div></div></div><div id="ml366.s2"><h2 id="_ml366_s2_">Recommendations for the scientific use of these probes</h2><p>Discovery of quorum sensing (QS) receptor agonists or other QS pathway modulators will permit more precise control of <i>Vibrio cholerae</i> QS through the perturbation of distinct steps within the signaling cascade. This, in turn, would enable elucidation of the underlying principles governing response regulator interactions utilized by intracellular transcriptional activators, such as the intracellular kinase LuxO. Upon phosphorylation, LuxO undergoes a number of conformational changes. The newly identified inhibitor probe may shed light on the nature of QS activators and possibly provide a clearer understanding of LuxO activities. <i>V. cholerae</i> LuxO is highly homologous to LuxO proteins in other <i>Vibrio</i> sp. and the larger class of NtrC transcriptional activators [<a class="bibr" href="#ml366.r1" rid="ml366.r1">1</a>]. If the probe targets a conserved domain, the probe may be useful to study two-component signaling pathways in a larger number of organisms [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>].</p><p>Crystallography efforts to visualize LuxO are underway, and this high-quality probe will be evaluated for possible co-crystallization. Concurrently, directed mutagenesis will be applied to understand how <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> interacts with LuxO. Identification of LuxO-inhibitor binding motifs will establish a framework for the development of antibacterial drugs designed to interfere with quorum sensing. This probe can also test the utility of quorum pathway activation as a means of treating cholera <i>via</i> reduction of the pathogen's virulence <i>in vivo</i>. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> can be tested in combination with CqsS agonists and could indicate the possibility of a potent and species-selective combination antibacterial therapy. There are several animal models available with which such studies may be conducted [<a class="bibr" href="#ml366.r3" rid="ml366.r3">3</a>-<a class="bibr" href="#ml366.r5" rid="ml366.r5">5</a>]. If such an approach is efficacious, these potential therapeutics, operating in a completely unexploited target space, would have enormous ramifications upon improving human health. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is currently not optimized for <i>in vivo</i> experiments but medicinal chemistry efforts can be directed towards improving this scaffold's ADME profile to facilitate animal studies.</p></div><div id="ml366.s3"><h2 id="_ml366_s3_">1. Introduction</h2><div id="ml366.s4"><h3>Scientific Rationale</h3><p>Bacteria utilize quorum sensing (QS) to assess the population density and species complexity of their environment and adapt their physiological behavior to the prevailing conditions. A large number of bacterial species utilize QS as a means to produce context specific gene products, such as virulence factors. Therefore, the ability to prevent virulence factor production could have a huge impact on human health. An example of a QS bacterium is the human pathogen <i>Vibrio cholerae</i>. The World Health Organization estimates that reported cases represent only 5–10% of the actual number of cholera incidents. There are an estimated 3 to 5 million cases that occur every year and approximately 120,000 deaths [<a class="bibr" href="#ml366.r6" rid="ml366.r6">6</a>]. These high case numbers persist despite the development of a vaccine and a simple treatment regimen. In addition to <i>V. cholerae</i>, there are at least six other <i>Vibrio</i> species that are human pathogens. It has been determined that <i>V. cholerae</i>, as well as other bacteria, rely on a two-component system to relay exogenous information to the cell interior. A transmembrane histidine kinase (<i>i.e.</i> sensor) and an internal response regulator are the primary constituents of these two-component systems [<a class="bibr" href="#ml366.r7" rid="ml366.r7">7</a>]. <i>V. cholerae</i> possess two parallel QS pathways. One pathway is responsible for interspecies communication wherein LuxPQ is the transmembrane receptor. A second, genus-specific pathway is controlled by the CqsS sensor [<a class="bibr" href="#ml366.r8" rid="ml366.r8">8</a>]. Both pathways converge upon a common intermediary, LuxO [<a class="bibr" href="#ml366.r9" rid="ml366.r9">9</a>]. <i>V. cholerae</i> is distinct from a number of bacterial species where activation of the QS pathway leads to inhibition of virulence factor production and not production of virulence factors.</p><p>The endogenous ligand of CqsS is the α-hydroxy ketone <b>1</b> (<a class="figpopup" href="/books/NBK189922/figure/ml366.f2/?report=objectonly" target="object" rid-figpopup="figml366f2" rid-ob="figobml366f2">Figure 1</a>), also known as cholera autoinducer 1 (CAI-1) [<a class="bibr" href="#ml366.r9" rid="ml366.r9">9</a>-<a class="bibr" href="#ml366.r10" rid="ml366.r10">10</a>]. Through careful studies of mutant CqsS receptors, it has been determined that CAI-1 inhibits His194 auto-phosphorylation of CqsS [<a class="bibr" href="#ml366.r11" rid="ml366.r11">11</a>]. The auto-phosphorylation of His194 is believed to initiate a phosphorelay sequence involving the intermediary transfer protein LuxU and terminates at the response regulator LuxO (<a class="figpopup" href="/books/NBK189922/figure/ml366.f3/?report=objectonly" target="object" rid-figpopup="figml366f3" rid-ob="figobml366f3">Figure 2</a>). LuxO is a member of the NtrC family of response regulators that require interaction with a σ-54 factor to activate transcription [<a class="bibr" href="#ml366.r12" rid="ml366.r12">12</a>]. LuxO binds DNA upstream of RNA polymerase and contains an inherent ATPase activity that is needed for changes to the transcriptional complex which involves DNA looping and subsequent formation of an open promoter complex [<a class="bibr" href="#ml366.r13" rid="ml366.r13">13</a>]. LuxO integrates the CqsS and AI-2 signaling pathways and a homologue has been found in all <i>Vibrio</i> species examined. There are species-specific differences on the number of pathways that feed into LuxO.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f2" co-legend-rid="figlgndml366f2"><a href="/books/NBK189922/figure/ml366.f2/?report=objectonly" target="object" title="Figure 1" class="img_link icnblk_img figpopup" rid-figpopup="figml366f2" rid-ob="figobml366f2"><img class="small-thumb" src="/books/NBK189922/bin/ml366f2.gif" src-large="/books/NBK189922/bin/ml366f2.jpg" alt="Figure 1. The Endogenous Ligand of the Vibrio cholerae Sensor Histidine Kinase CqsS, CAI-1." /></a><div class="icnblk_cntnt" id="figlgndml366f2"><h4 id="ml366.f2"><a href="/books/NBK189922/figure/ml366.f2/?report=objectonly" target="object" rid-ob="figobml366f2">Figure 1</a></h4><p class="float-caption no_bottom_margin">The Endogenous Ligand of the <i>Vibrio cholerae</i> Sensor Histidine Kinase CqsS, CAI-1. Cholera autoinducer-1 (CAI-1) </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f3" co-legend-rid="figlgndml366f3"><a href="/books/NBK189922/figure/ml366.f3/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml366f3" rid-ob="figobml366f3"><img class="small-thumb" src="/books/NBK189922/bin/ml366f3.gif" src-large="/books/NBK189922/bin/ml366f3.jpg" alt="Figure 2. The V. cholerae CqsS/CAI-1 Quorum Sensing Phosphorelay system." /></a><div class="icnblk_cntnt" id="figlgndml366f3"><h4 id="ml366.f3"><a href="/books/NBK189922/figure/ml366.f3/?report=objectonly" target="object" rid-ob="figobml366f3">Figure 2</a></h4><p class="float-caption no_bottom_margin">The <i>V. cholerae</i> CqsS/CAI-1 Quorum Sensing Phosphorelay system. At low cell density, there are insufficient amounts of CAI-1 to adequately bind CqsS. This leads to the production of AphA and the adoption of individual cell behaviors. At high cell density, <a href="/books/NBK189922/figure/ml366.f3/?report=objectonly" target="object" rid-ob="figobml366f3">(more...)</a></p></div></div><p>When CAI-1 is present in minute quantities, the phosphorelay system favors the phosphorylation of LuxO at Asp47 (<a class="figpopup" href="/books/NBK189922/figure/ml366.f3/?report=objectonly" target="object" rid-figpopup="figml366f3" rid-ob="figobml366f3">Figure 2</a>) [<a class="bibr" href="#ml366.r11" rid="ml366.r11">11</a>]. Phosphorylated LuxO up-regulates transcription of the small regulatory RNAs <i>qrr1-4</i>, which subsequently promote translation of AphA while simultaneously suppressing translation of the HapR regulator. AphA regulates genes that are beneficial to individual behaviors, while HapR regulates genes that promote group (quorum) behaviors. Another level of regulating the RNA is the RNA chaperone Hfq that base pairs with and destabilizes the <i>hapR</i> mRNA [<a class="bibr" href="#ml366.r12" rid="ml366.r12">12</a>]. When dense populations of <i>V. cholerae</i> synthesize and secrete sufficient quantities of CAI-1, this ligand will bind to CqsS and promote the production of HapR. The induction of HapR expression then allows the colonizing <i>V. cholerae</i> population to detach from the gut epithelium and vacate its host. Among the genes regulated by HapR is the expression of haemagglutinin protease (HapA) that facilitates the expulsion of <i>V. cholerae</i> from its human host [<a class="bibr" href="#ml366.r14" rid="ml366.r14">14</a>]. In most QS bacterial species, QS induces virulence factor production but <i>Vibrio cholerae</i> is distinct from other non-vibrio species because QS results in repression of virulence factor and biofilm production [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. From a therapeutic perspective, the artificial activation of CqsS or inhibition of LuxO or Hfq to promote HapR expression could lead to a new generation of anti-cholera treatments. A potential combinatorial therapeutic approach targeting multiple targets in the QS pathway could ensure effective and a genus-specific antimicrobial response.</p><p>Antagonism of LuxO has not been well studied in the literature thus far. The only known small molecule inhibitors of LuxO were reported after the initiation of this project [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. Derived from an aza-uracil scaffold, these compounds show moderate inhibition of LuxO activity (IC<sub>50</sub>'s range from 5 to 20 µM) in cellular assays. Further investigation of the most potent compound, (<a class="figpopup" href="/books/NBK189922/figure/ml366.f4/?report=objectonly" target="object" rid-figpopup="figml366f4" rid-ob="figobml366f4">Figure 3</a>, Aza-U), determined that these LuxO antagonists block ATPase hydrolysis and prevent subsequent transcriptional activation. Aza-U was selected as the positive control for all cell-based SAR assays in the post-HTS medicinal chemistry phase.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f4" co-legend-rid="figlgndml366f4"><a href="/books/NBK189922/figure/ml366.f4/?report=objectonly" target="object" title="Figure 3" class="img_link icnblk_img figpopup" rid-figpopup="figml366f4" rid-ob="figobml366f4"><img class="small-thumb" src="/books/NBK189922/bin/ml366f4.gif" src-large="/books/NBK189922/bin/ml366f4.jpg" alt="Figure 3. Aza-uracil-derived antagonists of LuxO ATPase activity." /></a><div class="icnblk_cntnt" id="figlgndml366f4"><h4 id="ml366.f4"><a href="/books/NBK189922/figure/ml366.f4/?report=objectonly" target="object" rid-ob="figobml366f4">Figure 3</a></h4><p class="float-caption no_bottom_margin">Aza-uracil-derived antagonists of LuxO ATPase activity. Aza-U (<i>4</i>) and its analogs have been shown to inhibit the ATPase activity of LuxO. Quorum-sensing modulation was measured in <i>V. cholera</i> strains BH1578 and BH1651 (see Section 2) and their respective <a href="/books/NBK189922/figure/ml366.f4/?report=objectonly" target="object" rid-ob="figobml366f4">(more...)</a></p></div></div><p>It is hoped that the identification of additional small molecule modulators of LuxO could elucidate the mechanisms of the latter steps underpinning the <i>V. cholerae</i> QS phosphorelay system. The additional chemical matter will also assist in the structural characterization of potential binding pockets and, in combination with a clearer understanding of how the transcriptional activation occurs, could guide development of new QS agonists as potential anti-cholera agents. Since all vibrios possess a LuxO homologue, LuxO inhibitors should be efficacious against all pathogenic vibrios. Aza-U compounds were found to inhibit LuxO activity in <i>V. harveyi</i> and <i>V. parahaemolyticus</i> [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>].</p></div></div><div id="ml366.s5"><h2 id="_ml366_s5_">2. Materials and Methods</h2><p>See subsections for a description of the materials and methods used for each assay.</p><div id="ml366.s6"><h3>Materials and Reagents</h3><ul><li class="half_rhythm"><div>CellTiter-Glo<sup>®</sup> Luminescent Cell Viability Assay was purchased from Promega (Catalog No. G7573; Madison, WI)</div></li></ul></div><div id="ml366.s7"><h3>Bacterial strains & Cell Lines</h3><p>The following cell lines were used in this study:</p><ul><li class="half_rhythm"><div><i>Vibrio cholerae</i> BH1578; a genetically modified strain lacking LuxS and CqsA autoinducer synthases that was provided by the Bassler lab. This strain was used in the primary assay.</div></li><li class="half_rhythm"><div><i>Vibrio cholerae</i> BH1651; a genetically modified strain with constitutively active LuxO that was provided by the Bassler lab.</div></li><li class="half_rhythm"><div><i>Vibrio cholerae</i> DH231; a genetically modified strain lacking the CqsS receptor that was provided by the Bassler lab.</div></li><li class="half_rhythm"><div><i>Vibrio cholerae</i> WN1103; a genetically modified strain lacking the LuxQ receptor that was provided by the Bassler lab.</div></li><li class="half_rhythm"><div>HeLa obtained from ATCC (Catalog Number CCL-2; Manassas, VA) is a human epithelial adenocarcinoma cell line used for mammalian cytotoxicity profiling</div></li></ul><p>Note: All of the <i>V. cholerae</i> strains also carry the heterologous <i>V. harveyi luxCDABE</i> luciferase operon</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t2"><a href="/books/NBK189922/table/ml366.t2/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figml366t2" rid-ob="figobml366t2"><img class="small-thumb" src="/books/NBK189922/table/ml366.t2/?report=thumb" src-large="/books/NBK189922/table/ml366.t2/?report=previmg" alt="Table 1. Strains of V. cholera used in assays." /></a><div class="icnblk_cntnt"><h4 id="ml366.t2"><a href="/books/NBK189922/table/ml366.t2/?report=objectonly" target="object" rid-ob="figobml366t2">Table 1</a></h4><p class="float-caption no_bottom_margin">Strains of <i>V. cholera</i> used in assays. </p></div></div></div><div id="ml366.s8"><h3>2.1. Assays</h3><p>A summary listing completed assays and their corresponding PubChem AID numbers is provided in <a href="#ml366.app1">Appendix A</a>. Refer to <a href="#ml366.app2">Appendix B</a> for the detailed assay protocols.</p><div id="ml366.s9"><h4>2.1.1. Primary assay – <i>V. cholerae</i> BH1578 bioluminescence inducer assay (AID 588346, AID 602243, AID 624270, AID 652239, AID 686929)</h4><p>A modified strain of <i>Vibrio cholerae</i> used in this assay uses light production to indicate quorum sensing induction. <i>Vibrio cholerae</i> is not naturally bioluminescent but the closely related species <i>Vibrio harveyi</i> produces light when the population is at a high density (i.e. a quorum is sensed). The heterologous <i>Vibrio harveyi</i> luciferase operon (<i>luxCDABE</i>) was cloned into the <i>Vibrio cholerae</i> C6706 O1 El Tor bacterial strain on the pBB1 cosmid to create a bioluminescence assay strain. This operon is activated by the endogenous <i>V. cholerae</i> quorum sensing pathway [<a class="bibr" href="#ml366.r15" rid="ml366.r15">15</a>]. The BH1578 strain is a cqsA, luxS double mutant that lacks both autoinducer synthases (CAI-1 and AI-2). BH1578 does not generate light in the absence of exogenous autoinducers but bioluminescence can be stimulated up to 10,000-fold by adding 1 µM (saturating) CAI-1. On day 0, a colony of bacteria was picked into 50 mL Luria Broth with 10 µg/mL tetracycline and cultured overnight at 30 °C. On day 1, bacterial density was determined by spectrometry, and the OD600 was adjusted to 0.3. 20 µL of Luria Broth with 10 µg/mL tetracycline was added per well into white, opaque 384 well plates. Compounds and controls were added by pin transfer method. The HTS used 150 nL of compound for screening at 20 µM, and the retest assays used 100 nL of compound. After 6 hours, the luminescence signal was determined with the Perkin-Elmer EnVision plate reader. In addition to luminescence, the confluency of each well was measured at an absorbance of 600 nM. Primary HTS data were analyzed in Genedata Screener Assay Analyzer. All values were normalized against DMSO treated samples and the positive control (1 µM CAI-1, CID 24892809). For the HTS, the average of two replicates was used to rank order activity and to choose compounds for retests. For dose studies, percent (%) activity was determined for each concentration, and the concentration response curves (CRCs) were generated with Genedata Screener's Condoseo.</p></div><div id="ml366.s10"><h4>2.1.2. Secondary assay – HeLa cytotoxicity assay (AID 624140, AID 686928)</h4><p>HeLa cells were treated with compounds for 24 hours, and then cell viability was measured using the CellTiter-Glo Assay (Promega), a luciferase-based reagent that measures cellular ATP levels. The compounds were tested at different concentrations to determine IC<sub>50</sub> values. Compounds that were inactive (IC<sub>50</sub> ≥ 30 µM) in this assay were considered for probe development. Data were normalized against DMSO in Genedata Screener's Assay Analyzer. Curves were generated with Genedata Screener's Condoseo and showed percent (%) activity for the individual doses.</p></div><div id="ml366.s11"><h4>2.1.3. Secondary assay – <i>V. cholerae</i> BH1651 LuxO inhibitor assay (AID 624254, AID 624269, AID 652289)</h4><p>A modified strain of <i>Vibrio cholerae</i> used in this assay uses light production to indicate quorum sensing induction. <i>Vibrio cholerae</i> is not naturally bioluminescent but the closely related species <i>Vibrio harveyi</i> produces light when the population is at a high density (i.e. a quorum is sensed). The heterologous <i>Vibrio harveyi</i> luciferase operon (<i>luxCDABE</i>) was cloned into the <i>Vibrio cholerae</i> C6706 O1 El Tor bacterial strain on the pBB1 cosmid to create a bioluminescence assay strain. This operon is activated by the endogenous <i>V. cholerae</i> quorum sensing pathway [<a class="bibr" href="#ml366.r15" rid="ml366.r15">15</a>]. The BH1651 strain is a luxO<sup>D47E</sup> mutant where LuxO<sup>D47E</sup> mimics the behavior of phosphorylated LuxO, rendering LuxO<sup>D47E</sup> constitutively active within the QS pathway. BH1651 does not generate light but any compound that inhibits LuxO or works downstream of LuxO will induce light production. On day 0, a colony of bacteria was picked into 50 mL Luria Broth with 10 µg/mL tetracycline and cultured overnight at 30 °C. On day 1, bacterial density was determined by spectrometry, and the OD<sub>600</sub> was adjusted to 0.3. 20 µL of Luria Broth with 10 µg/mL tetracycline was added per well into white, opaque 384 well plates. Compounds and controls were added by pin transfer method. After 6 hours, the luminescence signal was determined with the Perkin-Elmer EnVision plate reader. In addition to luminescence, the confluency of each well was measured at an absorbance of 600 nM. Data were analyzed in Genedata Screener Assay Analyzer. All values were normalized against DMSO and 40 µM Aza-U (positive control) treated samples. Percent (%) activity was determined for each concentration, and the concentration response curves (CRCs) were generated with Genedata Screener's Condoseo.</p></div><div id="ml366.s12"><h4>2.1.4. Secondary assay – <i>V. cholerae</i> DH231 sensor mechanism assay (AID 624281, AID 686931)</h4><p>A modified strain of <i>Vibrio cholerae</i> used in this assay uses light production to indicate quorum sensing induction. <i>Vibrio cholerae</i> is not naturally bioluminescent but the closely related species <i>Vibrio harveyi</i> produces light when the population is at a high density (i.e. a quorum is sensed). The heterologous <i>Vibrio harveyi</i> luciferase operon (<i>luxCDABE</i>) was cloned into the <i>Vibrio cholerae</i> C6706 O1 El Tor bacterial strain on the pBB1 cosmid to create a bioluminescence assay strain. This operon is activated by the endogenous <i>V. cholerae</i> quorum sensing pathway [<a class="bibr" href="#ml366.r15" rid="ml366.r15">15</a>]. The DH231 strain is a luxS and cqsS double deletion mutant. DH231 does not generate light but any compound that agonizes the receptor LuxQ will induce light production, and CqsS agonists will have no activity in this assay. On day 0, a colony of bacteria was picked into 50 mL Luria Broth with 10 µg/mL tetracycline and cultured overnight at 30 °C. On day 1, bacterial density was determined by spectrometry, and the OD<sub>600</sub> was adjusted to 0.3. 20 µL of Luria Broth with 10 µg/mL tetracycline was added per well into white, opaque 384 well plates. Compounds and controls were added by pin transfer method. After 6 hours, the luminescence signal was determined with the Perkin-Elmer EnVision plate reader. In addition to luminescence, the confluency of each well was measured at an absorbance of 600 nM. Data were analyzed in Genedata Screener Assay Analyzer. All values were normalized against DMSO and 40 µM Aza-U (positive control) treated samples. Percent (%) activity was determined for each concentration, and the concentration response curves (CRCs) were generated with Genedata Screener's Condoseo.</p></div><div id="ml366.s13"><h4>2.1.5. Secondary assay – <i>V. cholerae</i> WN1103 sensor mechanism assay (AID 624275, AID 686390)</h4><p>A modified strain of <i>Vibrio cholerae</i> used in this assay uses light production to indicate quorum sensing induction. <i>Vibrio cholerae</i> is not naturally bioluminescent but the closely related species <i>Vibrio harveyi</i> produces light when the population is at a high density (i.e. a quorum is sensed). The heterologous <i>Vibrio harveyi</i> luciferase operon (<i>luxCDABE</i>) was cloned into the <i>Vibrio cholerae</i> C6706 O1 El Tor bacterial strain on the pBB1 cosmid to create a bioluminescence assay strain. This operon is activated by the endogenous <i>V. cholerae</i> quorum sensing pathway [<a class="bibr" href="#ml366.r15" rid="ml366.r15">15</a>]. The WN1103 strain is a luxPQ and cqsA double deletion mutant. DH231 does not generate light but any compound that agonizes the CqsS receptor will induce light production and LuxQ agonists will have no activity in this assay. On day 0, a colony of bacteria was picked into 50 mL Luria Broth with 10 µg/mL tetracycline and cultured overnight at 30 °C. On day 1, bacterial density was determined by spectrometry, and the OD<sub>600</sub> was adjusted to 0.3. 20 µL of Luria Broth with 10 µg/mL tetracycline was added per well into white, opaque 384 well plates. Compounds and controls were added by pin transfer method. After 6 hours, the luminescence signal was determined with the Perkin-Elmer EnVision plate reader. In addition to luminescence, the confluency of each well was measured at an absorbance of 600 nM. Data were analyzed in Genedata Screener Assay Analyzer. All values were normalized against DMSO and 40 µM Aza-U (positive control) treated samples. Percent (%) activity was determined for each concentration, and the concentration response curves (CRCs) were generated with Genedata Screener's Condoseo.</p></div><div id="ml366.s14"><h4>2.1.6. Secondary assay – <i>V. cholerae</i> SLS353 qrr4:GFP fluorescence reporter assay (AID 652219, AID 686942)</h4><p>A modified strain of <i>Vibrio cholerae</i> used in this assay uses fluorescence to indicate qrr4 sRNA transcription [<a class="bibr" href="#ml366.r15" rid="ml366.r15">15</a>]. The SLS353 strain is a luxO<sup>D47E</sup> mutant strain containing the pSLS4 plasmid where the qrr4 promoter drives GFP expression. LuxO<sup>D47E</sup> mimics the behavior of phosphorylated LuxO, rendering LuxO<sup>D47E</sup> constitutively active. This leads to steady levels of qrr4 promoter-driven GFP. Any compound that inhibits LuxO or works downstream of LuxO will decrease qrr4:GFP expression. Since the GFP protein tends to be more stable than luciferase, the compound incubation is increased from 6 to 16 hours. On day 0, a colony of bacteria was picked into 50 mL Luria Broth with 100 µg/mL kanamycin and cultured overnight at 30 °C. On day 1, bacterial density was determined by spectrometry, and the OD<sub>600</sub> was adjusted to 0.3. 20 µL of Luria Broth with 100 µg/mL kanamycin was added per well into white, opaque 384 well plates. Compounds and controls were added by pin transfer method. After 16 hours, the fluorescence signal was determined with the Perkin-Elmer EnVision plate reader using 480 nM excitation and 509nM emission wavelength spectra. All values were compared to DMSO and 40 µM Aza-U (positive control) treated samples. The concentration response curves (CRCs) were generated with GraphPad Prism 6.</p></div><div id="ml366.s15"><h4>2.1.7. Secondary assay – LuxO <i>in vitro</i> ATPase assay (AID 686936)</h4><p>A modified coupled-enzyme assay measured the rate of ATP hydrolysis by LuxO<i><sup>D47E</sup></i> [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. Briefly, ADP released from ATP by LuxO<i><sup>D47E</sup></i> is reacted with phosphoenolpyruvate (PEP) to form pyruvate using pyruvate kinase (PK). Pyruvate is reacted with NADH to form NAD and lactate using lactate dehydrogenase (LDH). The rate of NAD production is followed at 340 nm using a spectrophotometer. ATP hydrolysis rates were inferred from the absorbance change observed (ε<sub>NADH,340</sub> -ε-<sub>NAD,340</sub> = 6220 M<sup>-1</sup> cm<sup>-1</sup> for NADH) [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. The rates of ATP hydrolysis by LuxO<i><sup>D47E</sup></i> were measured in reactions containing 100 mM Sodium phosphate buffer pH 7.4, 5 mM MgCl<sub>2</sub>, 0.2 mM NADH, 1 mM PEP, 5–20 units of PK/LDH mix (Sigma), and 10 mM LuxO<i><sup>D47E</sup></i>. ATP and inhibitors were added to the reactions at indicated concentrations. The rate of ATP hydrolysis was monitored for 5 minutes. Data were fitted using GraphPad Prism to obtain the kinetic parameters. Percent ATPase inhibition was calculated.</p></div></div><div id="ml366.s16"><h3>2.2. Probe Chemical Characterization</h3><p>After preparation as described in <a href="#ml366.s17">Section 2.3</a>, the probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was analyzed by UPLC, <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy, and high-resolution mass spectrometry. The data obtained from NMR and mass spectroscopy are consistent with the structure of the probe, and UPLC indicates an isolated purity of greater than 98%. The complete synthetic protocol is provided in <a href="#ml366.app3">Appendix C</a>, and associated spectral data are provided in <a href="#ml366.app5">Appendix E</a>.</p><p>The solubility of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was experimentally determined to be less than 1 µM in phosphate buffered saline (PBS) with 1% (v/v) DMSO. Solubility was also measured in the Luria Broth (LB) media used in the primary assay. <a class="figpopup" href="/books/NBK189922/table/ml366.t3/?report=objectonly" target="object" rid-figpopup="figml366t3" rid-ob="figobml366t3">Table 2</a> summarizes the solubility of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and several analogs in both PBS and LB media. In general, LB media is a better solvent than PBS for these compounds.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t3"><a href="/books/NBK189922/table/ml366.t3/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figml366t3" rid-ob="figobml366t3"><img class="small-thumb" src="/books/NBK189922/table/ml366.t3/?report=thumb" src-large="/books/NBK189922/table/ml366.t3/?report=previmg" alt="Table 2. Solubility of ML366 and Analogs in PBS and LB Assay Media." /></a><div class="icnblk_cntnt"><h4 id="ml366.t3"><a href="/books/NBK189922/table/ml366.t3/?report=objectonly" target="object" rid-ob="figobml366t3">Table 2</a></h4><p class="float-caption no_bottom_margin">Solubility of ML366 and Analogs in PBS and LB Assay Media. </p></div></div><p>The probe is stable in PBS solution (>99% remaining after a 48-hour incubation at 23 °C). The data from the PBS stability assay is provided in <a class="figpopup" href="/books/NBK189922/figure/ml366.f5/?report=objectonly" target="object" rid-figpopup="figml366f5" rid-ob="figobml366f5">Figure 4</a>. The probe is also stable to human plasma with greater than 75% remaining after incubation at 37 °C for 5 hours. Murine plasma degrades the probe rapidly as less than 1% of compound was remaining after a 5-hour incubation. No significant reaction with glutathione (GSH) was observed for <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>. <a class="figpopup" href="/books/NBK189922/table/ml366.t4/?report=objectonly" target="object" rid-figpopup="figml366t4" rid-ob="figobml366t4">Table 3</a> summarizes the various stability assays performed. Experimental procedures for all analytical assays are provided in <a href="#ml366.app4">Appendix D</a>. The physical properties of probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> are summarized in <a class="figpopup" href="/books/NBK189922/table/ml366.t5/?report=objectonly" target="object" rid-figpopup="figml366t5" rid-ob="figobml366t5">Table 4</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f5" co-legend-rid="figlgndml366f5"><a href="/books/NBK189922/figure/ml366.f5/?report=objectonly" target="object" title="Figure 4" class="img_link icnblk_img figpopup" rid-figpopup="figml366f5" rid-ob="figobml366f5"><img class="small-thumb" src="/books/NBK189922/bin/ml366f5.gif" src-large="/books/NBK189922/bin/ml366f5.jpg" alt="Figure 4. Stability of Probe ML366 in PBS Buffer (pH 7.4, 23°C)." /></a><div class="icnblk_cntnt" id="figlgndml366f5"><h4 id="ml366.f5"><a href="/books/NBK189922/figure/ml366.f5/?report=objectonly" target="object" rid-ob="figobml366f5">Figure 4</a></h4><p class="float-caption no_bottom_margin">Stability of Probe ML366 in PBS Buffer (pH 7.4, 23°C). </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t4"><a href="/books/NBK189922/table/ml366.t4/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml366t4" rid-ob="figobml366t4"><img class="small-thumb" src="/books/NBK189922/table/ml366.t4/?report=thumb" src-large="/books/NBK189922/table/ml366.t4/?report=previmg" alt="Table 3. Plasma Stability and Plasma Binding of ML366." /></a><div class="icnblk_cntnt"><h4 id="ml366.t4"><a href="/books/NBK189922/table/ml366.t4/?report=objectonly" target="object" rid-ob="figobml366t4">Table 3</a></h4><p class="float-caption no_bottom_margin">Plasma Stability and Plasma Binding of ML366. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t5"><a href="/books/NBK189922/table/ml366.t5/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml366t5" rid-ob="figobml366t5"><img class="small-thumb" src="/books/NBK189922/table/ml366.t5/?report=thumb" src-large="/books/NBK189922/table/ml366.t5/?report=previmg" alt="Table 4. Summary of Probe Properties Computed for ML366." /></a><div class="icnblk_cntnt"><h4 id="ml366.t5"><a href="/books/NBK189922/table/ml366.t5/?report=objectonly" target="object" rid-ob="figobml366t5">Table 4</a></h4><p class="float-caption no_bottom_margin">Summary of Probe Properties Computed for ML366. </p></div></div></div><div id="ml366.s17"><h3>2.3. Probe Preparation</h3><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and most associated analogs were prepared according to the route outlined in <a class="figpopup" href="/books/NBK189922/figure/ml366.f6/?report=objectonly" target="object" rid-figpopup="figml366f6" rid-ob="figobml366f6">Scheme 1</a>. Commercially available 2-amino-oxadiazole <b>6</b> was reacted with an excess of cyclohexylcarboxylic acid under peptide coupling conditions. Upon complete consumption of starting material, the product was selectively precipitated by the addition of water.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f6" co-legend-rid="figlgndml366f6"><a href="/books/NBK189922/figure/ml366.f6/?report=objectonly" target="object" title="Scheme 1" class="img_link icnblk_img figpopup" rid-figpopup="figml366f6" rid-ob="figobml366f6"><img class="small-thumb" src="/books/NBK189922/bin/ml366f6.gif" src-large="/books/NBK189922/bin/ml366f6.jpg" alt="Scheme 1. Synthesis of Probe ML366." /></a><div class="icnblk_cntnt" id="figlgndml366f6"><h4 id="ml366.f6"><a href="/books/NBK189922/figure/ml366.f6/?report=objectonly" target="object" rid-ob="figobml366f6">Scheme 1</a></h4><p class="float-caption no_bottom_margin">Synthesis of Probe ML366. </p></div></div><p>Full experimental details for the preparation of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> are provided in <a href="#ml366.app3">Appendix C</a>.</p></div></div><div id="ml366.s18"><h2 id="_ml366_s18_">3. Results</h2><div id="ml366.s19"><h3>Probe attributes</h3><ul><li class="half_rhythm"><div>Induces light production in <i>V. cholerae</i> strain BH1578 with EC<sub>50</sub> ≤ 10 µM</div></li><li class="half_rhythm"><div>Induces light production in <i>V. cholerae</i> strains BH1651, DH231 & WN1103</div></li><li class="half_rhythm"><div>Non-toxic to HeLa cells with IC<sub>50</sub> ≥ 30 µM</div></li></ul><p>The current project utilizes several genetically modified strains of the human pathogen <i>Vibrio cholerae</i> in an effort to identify potential activators of the <i>V. cholerae</i> quorum sensing (QS) network. The MLSMR collection of 352,083 compounds was examined for possible QS activators, using <i>V. cholerae</i> BH1578 as the primary test strain. In the <i>V. cholerae</i> BH1578 strain, the <i>V. harveyi</i> luxCDABE (luciferase) operon was introduced as a cosmid, and the operon is activated by endogenous mechanisms to elicit light upon reaching a quorum. In addition, the BH1578 strain is a <i>cqsA, luxS</i> double deletion mutant that lacks the ability to produce any endogenous autoinducers of QS. Therefore, light production can only occur in response to an activating screening compound. Secondary assays utilizing additional <i>V. cholerae</i> mutants were included in order to triage active compounds by their potential mode of action. Based on their behavior in the various secondary assays, compounds were categorized as an agonist of either CqsS or LuxQ; an inhibitor of LuxO; or as an inhibitor of Hfq.</p><p>Analysis of the primary screening data revealed that approximately 500 compounds could activate the <i>V. cholerae</i> QS pathway. Re-evaluation of these compounds in a dose-response format led to the selection of 26 compounds for subsequent examination as commercially-made dry powders. Based on their cellular potency in BH1578 and low toxicity towards HeLa cells, two scaffolds (CID 4443990 and CID 665390) were selected for further development as LuxO inhibitors. The optimization of CID 665390 to <a href="/pcsubstance/?term=ML370[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML370</a> was undertaken by the University of Kansas MLPCN Chemistry Center, and the results of those studies will be reported separately.</p><p>The substituted 2-amino-oxadiazole CID 4443990 (<a class="figpopup" href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" rid-figpopup="figml366f7" rid-ob="figobml366f7">Figure 5</a>) is an activator of <i>V. cholerae</i> QS with a measured AC<sub>50</sub> = 5.1 µM for the commercial material. Re-synthesized CID 4443990 is equipotent to the commercial sample (AC<sub>50</sub> = 6.1 µM), and neither demonstrated observable toxicity to HeLa cells (IC<sub>50</sub> >35 µM). Analogs of CID 4443990 were designed, prepared, and evaluated for QS activation. The results of the structure-activity relationship (SAR) studies are summarized in <a href="#ml366.s23">Section 3.4</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f7" co-legend-rid="figlgndml366f7"><a href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" title="Figure 5" class="img_link icnblk_img figpopup" rid-figpopup="figml366f7" rid-ob="figobml366f7"><img class="small-thumb" src="/books/NBK189922/bin/ml366f7.gif" src-large="/books/NBK189922/bin/ml366f7.jpg" alt="Figure 5. Representative Dose Response Curves for Samples of CID 4443990." /></a><div class="icnblk_cntnt" id="figlgndml366f7"><h4 id="ml366.f7"><a href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" rid-ob="figobml366f7">Figure 5</a></h4><p class="float-caption no_bottom_margin">Representative Dose Response Curves for Samples of CID 4443990. CID 4443990 was tested across a range of concentrations up to 35 µM in the primary assay and the BH1651 assay. Concentration response curves were generated with Genedata Screener <a href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" rid-ob="figobml366f7">(more...)</a></p></div></div></div><div id="ml366.s20"><h3>3.1. Summary of Screening Results</h3><p>As described above, the Molecular Libraries and Small Molecules Repository (MLSMR) collection of 352,083 unique compounds were tested at a single concentration (20 µM) for their ability to induce the production of luciferase by BH1578, thus indicating successful activation of the QS signaling pathway. 553 compounds were active at 20 µM, representing a nominal hit rate of 0.15%.</p><p>The active compounds were then re-tested in a dose-response format, wherein only 2 compounds actually met or exceeded the project requirement of AC<sub>50</sub> ≤ 1.0 µM. However, the low success rate of the primary assay prompted us to expand the primary assay cut-off to include substances with AC<sub>50</sub> ≤ 10 µM.</p><p>Subsequently, dry powders for 26 compounds were procured for re-testing. After purity analysis and structural confirmation by NMR spectroscopy, these substances were screened according to the workflow outlined in <a class="figpopup" href="/books/NBK189922/figure/ml366.f8/?report=objectonly" target="object" rid-figpopup="figml366f8" rid-ob="figobml366f8">Figure 6</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f8" co-legend-rid="figlgndml366f8"><a href="/books/NBK189922/figure/ml366.f8/?report=objectonly" target="object" title="Figure 6" class="img_link icnblk_img figpopup" rid-figpopup="figml366f8" rid-ob="figobml366f8"><img class="small-thumb" src="/books/NBK189922/bin/ml366f8.gif" src-large="/books/NBK189922/bin/ml366f8.jpg" alt="Figure 6. Critical Path for Probe Development." /></a><div class="icnblk_cntnt" id="figlgndml366f8"><h4 id="ml366.f8"><a href="/books/NBK189922/figure/ml366.f8/?report=objectonly" target="object" rid-ob="figobml366f8">Figure 6</a></h4><p class="float-caption no_bottom_margin">Critical Path for Probe Development. </p></div></div><p>The assay progression outlined in <a class="figpopup" href="/books/NBK189922/figure/ml366.f8/?report=objectonly" target="object" rid-figpopup="figml366f8" rid-ob="figobml366f8">Figure 6</a> assessed the activation of QS pathways in several <i>V. cholerae</i> strains: BH1578, BH1651, and SLS353. CID 4443990 emerged as a promising LuxO inhibitor and was subsequently prioritized for development. A number of analogs were prepared and assayed for QS activation. The results of the SAR investigation are presented in detail in <a href="#ml366.s23">Section 3.4</a>.</p></div><div id="ml366.s21"><h3>3.2. Representative Dose Response Curves for Probe ML366</h3><div id="ml366.f9" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20ML366%20Induces%20Quorum%20Sensing%20via%20LuxO%20ATPase%20Inhibition%20without%20Toxicity.&p=BOOKS&id=189922_ml366f9.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f9.jpg" alt="Figure 7. ML366 Induces Quorum Sensing via LuxO ATPase Inhibition without Toxicity." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">ML366 Induces Quorum Sensing via LuxO ATPase Inhibition without Toxicity</span></h3><div class="caption"><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was tested across a range of concentrations up to 35 µM in the primary BH1578 assay, the SLS353 qrr4:GFP reporter assay, the <i>in vitro</i> LuxO ATPase assay and a HeLa cytotoxicity assay. Concentration response curves were generated with Genedata Screener Condoseo and show normalized percent activity for the individual doses. DH231 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686931" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686931</a>), IC<sub>50</sub> = 2.1 µM (<i>A</i>); SLS353 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686942" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686942</a>) (<i>B</i>); <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>
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<i>in vitro</i> LuxO ATPase assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686936" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686936</a>) (<i>C</i>); <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> HeLa CellTiter-Glo (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686928</a>), IC<sub>50</sub> ≥ 35 µM (D). ○ = replicate 1, △ = replicate 2. RFU=relative fluorescence unit.</p></div></div></div><div id="ml366.s22"><h3>3.3. Scaffold/Moiety Chemical Liabilities</h3><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> possesses no obvious chemical liabilities, and a phosphate-buffered saline solution of the probe showed no significant decomposition over a 48-hour period. In addition, glutathione did not react with the probe appreciably after six hours. Exposure to human plasma did not affect the probe, but it decomposed rapidly upon treatment with murine plasma. These results are summarized in <a href="#ml366.s16">Section 2.2</a>.</p><p>A search of PubChem for <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> shows that this compound has been evaluated in a total of 583 assays. There are 15 assays unrelated to this project in which <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> showed a reported AC<sub>50</sub> below 20 µM. <a class="figpopup" href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object" rid-figpopup="figml366t6" rid-ob="figobml366t6">Table 5</a> lists the 15 assays, the PubChem activity outcome, and the measured activity of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>. It should be noted that the assay results include active, inactive or inconclusive categories. Inconclusive data are cases where data has too few data points or no dose dependent response. By viewing the dose curves, the term ‘active’ proves to be misleading for some of the results. For example, the NPC activator assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/485313" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 485313</a>) dose curve reveals a partial curve with only 4 data points where only the top concentration shows an appreciable increase in signal that does not meet 100% activity for that assay. The Rab9 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/484297" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 484297</a>) shows a potent activation of signal for this luciferase reporter but there has been no subsequent data reported for this compound within this particular project nearly three years after this data was submitted to PubChem (as of 23 July 2013).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t6"><a href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figml366t6" rid-ob="figobml366t6"><img class="small-thumb" src="/books/NBK189922/table/ml366.t6/?report=thumb" src-large="/books/NBK189922/table/ml366.t6/?report=previmg" alt="Table 5. PubChem Assays Reporting Dose-Dependent Activity of ML366." /></a><div class="icnblk_cntnt"><h4 id="ml366.t6"><a href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object" rid-ob="figobml366t6">Table 5</a></h4><p class="float-caption no_bottom_margin">PubChem Assays Reporting Dose-Dependent Activity of ML366. </p></div></div><p>The mild inhibition of firefly luciferase (<a class="figpopup" href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object" rid-figpopup="figml366t6" rid-ob="figobml366t6">Table 5, entry 4</a>) by <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is not a concern for this project. Despite its nominal potency of 2.7 µM against purified enzyme, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> only achieves ~35% maximum inhibition of function. There is no indication of firefly luciferase inhibition in a cellular context, and the <i>V. cholerae</i> assays studied in the current project express the naturally occurring <i>V. harveyi</i> luciferase protein. An alignment of the firefly versus <i>V. harveyi</i> protein sequences using an online protein alignment tool, CLUSTAL Omega (<a href="http://www.ebi.ac.uk/Tools/msa/clustalo/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.ebi.ac.uk/Tools/msa/clustalo/</a>), indicates that the eukaryotic and prokaryotic luciferases do not possess significant homology (data not shown). In addition, the primary assay relies upon a gain-of-signal readout; potent luciferase inhibitors would inherently be removed by the assay design. Finally, our HeLa cytotoxicity assay uses CellTiter Glo, which utilizes firefly luciferase and there is no reduction in signal observed, even at the top concentration of 35 µM (<a class="figpopup" href="/books/NBK189922/figure/ml366.f9/?report=objectonly" target="object" rid-figpopup="figml366f9" rid-ob="figobml366f9">Figure 7D</a>).</p><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was screened for toxicity towards HeLa cells, and no adverse effects were observed below 35 µM concentration. The reported activity against ELG1 in modified HEK293T cells (<a class="figpopup" href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object" rid-figpopup="figml366t6" rid-ob="figobml366t6">Table 5, entry 10</a>) does not suggest mammalian toxicity because the treatment leads to an increase in luciferase signal.</p><p>A structure-based search (80% similarity to <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>) in SciFinder reveals that several related 2-amino-thiadiazoles are potent and selective EP<sub>3</sub> receptor antagonists [<a class="bibr" href="#ml366.r17" rid="ml366.r17">17</a>]. The function of the EP<sub>3</sub> receptor has not been fully elucidated, but it is implicated in gastric acid secretion as well as uterine, bladder, and smooth muscle contractions [<a class="bibr" href="#ml366.r17" rid="ml366.r17">17</a>]. <a class="figpopup" href="/books/NBK189922/figure/ml366.f10/?report=objectonly" target="object" rid-figpopup="figml366f10" rid-ob="figobml366f10">Figure 8</a> shows representative aminothiadiazoles.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f10" co-legend-rid="figlgndml366f10"><a href="/books/NBK189922/figure/ml366.f10/?report=objectonly" target="object" title="Figure 8" class="img_link icnblk_img figpopup" rid-figpopup="figml366f10" rid-ob="figobml366f10"><img class="small-thumb" src="/books/NBK189922/bin/ml366f10.gif" src-large="/books/NBK189922/bin/ml366f10.jpg" alt="Figure 8. Aminothiadiazole-containing Inhibitors of the EP3 Receptor." /></a><div class="icnblk_cntnt" id="figlgndml366f10"><h4 id="ml366.f10"><a href="/books/NBK189922/figure/ml366.f10/?report=objectonly" target="object" rid-ob="figobml366f10">Figure 8</a></h4><p class="float-caption no_bottom_margin">Aminothiadiazole-containing Inhibitors of the EP<sub>3</sub> Receptor. </p></div></div><p>A similar search (80% structural similarity) of the Thomson Reuters Integrity database did not identify any publications or clinical trials describing the probe or related compounds.</p></div><div id="ml366.s23"><h3>3.4. SAR Tables</h3><p>In order to investigate the activity of the hit compound CID 4443990, 29 structurally related analogs were synthesized and evaluated for their ability to initiate the QS pathway in the BH1578 <i>V. cholerae</i> strain. The biological assay data of these analogs are presented in <a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Tables 6</a>-<a class="figpopup" href="/books/NBK189922/table/ml366.t9/?report=objectonly" target="object" rid-figpopup="figml366t9" rid-ob="figobml366t9">8</a>. Characterization data (<sup>1</sup>H NMR spectra and UPLC chromatograms) of these analogs are provided in <a href="#ml366.app7">Appendix G</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t7"><a href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figml366t7" rid-ob="figobml366t7"><img class="small-thumb" src="/books/NBK189922/table/ml366.t7/?report=thumb" src-large="/books/NBK189922/table/ml366.t7/?report=previmg" alt="Table 6. Examination of the Benzodioxane System." /></a><div class="icnblk_cntnt"><h4 id="ml366.t7"><a href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-ob="figobml366t7">Table 6</a></h4><p class="float-caption no_bottom_margin">Examination of the Benzodioxane System. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t9"><a href="/books/NBK189922/table/ml366.t9/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img figpopup" rid-figpopup="figml366t9" rid-ob="figobml366t9"><img class="small-thumb" src="/books/NBK189922/table/ml366.t9/?report=thumb" src-large="/books/NBK189922/table/ml366.t9/?report=previmg" alt="Table 8. Different Combinations of Amides and Benzodioxane Replacements." /></a><div class="icnblk_cntnt"><h4 id="ml366.t9"><a href="/books/NBK189922/table/ml366.t9/?report=objectonly" target="object" rid-ob="figobml366t9">Table 8</a></h4><p class="float-caption no_bottom_margin">Different Combinations of Amides and Benzodioxane Replacements. </p></div></div><p>The initial oxadiazole hit CID 4443990 shows acceptable potency in the primary BH1578 cell line and is capable of light induction superior to the Aza-U positive control (<a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Table 6, entry 1</a>). Enhancing cellular potency and aqueous solubility (<i>cf.</i>
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<a href="#ml366.s16">Section 2.2</a>) were prioritized goals for SAR exploration. The murine plasma instability, tentatively attributed to the amide functionality, was deemed a secondary objective for optimization.</p><p>It was hypothesized that the 1,4-benzodioxane heterocycle is a contributing factor for the poor aqueous solubility of the hit. Accordingly, less substituted aromatic rings were evaluated in place of the larger ring system. Reducing this group to an anisole (<a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Table 6, entries 2-4</a>) or chlorobenzene (<a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Table 6, entries 5-7</a>) affords minor gains in solubility, with the <i>ortho</i>-substituted analogs being the most soluble compounds. Presumably, disrupting the planarity of the overall structure contributes to the higher solubility. Two compounds from this phenyl series elicit only a partial response in BH1578 cells (<a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Table 6, entries 2 & 4</a>), and the remaining four are inactive. Introduction of pyridyl and cyclopentyl rings produces soluble, but inactive, compounds (<a class="figpopup" href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object" rid-figpopup="figml366t7" rid-ob="figobml366t7">Table 6, entries 8-9</a>).</p><p>Examination of the cyclohexyl amide was undertaken next and the results are summarized in <a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7</a>. While retaining the benzodioxane portion, a variety of cycloalkane amides were prepared (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 2-8</a>). The cycloheptyl amide (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entry 5</a>) was the largest ring evaluated and is the only compound of this amide series displaying any cellular activity. Surprisingly, reducing the ring size significantly increases aqueous solubility (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 2-3</a>). This finding, as well as the high solubility of the piperidine and tetrahydropyran analogs (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 6-7</a>), suggests that the benzodioxane is not the primary contributor to the hit's poor solubility. The aliphatic amides and amine prepared (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 9-11</a>) are inactive in the primary assay as are the phenyl sulfonamides (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 12-13</a>). Imine intermediates and the free amine were also evaluated (<a class="figpopup" href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-figpopup="figml366t8" rid-ob="figobml366t8">Table 7, entries 14-16</a>), but none of these compounds show measurable induction of <i>V. cholera</i> quorum sensing.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t8"><a href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figml366t8" rid-ob="figobml366t8"><img class="small-thumb" src="/books/NBK189922/table/ml366.t8/?report=thumb" src-large="/books/NBK189922/table/ml366.t8/?report=previmg" alt="Table 7. Biological Activity of Various Amides and Amine Substituents." /></a><div class="icnblk_cntnt"><h4 id="ml366.t8"><a href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object" rid-ob="figobml366t8">Table 7</a></h4><p class="float-caption no_bottom_margin">Biological Activity of Various Amides and Amine Substituents. </p></div></div><p>Several compounds bearing various combinations of amides and benzodioxane replacements were synthesized (<a class="figpopup" href="/books/NBK189922/table/ml366.t9/?report=objectonly" target="object" rid-figpopup="figml366t9" rid-ob="figobml366t9">Table 8</a>). While most have increased aqueous solubility, none are as efficacious as the original hit.</p><p>The SAR is flat with regards to cellular potency; modification of the cyclohexyl amide or the benzodioxane region strongly diminishes quorum sensing agonism. However, aqueous solubility is readily obtained <i>via</i> reducing the carbon content of the amide. Because the more soluble compounds underperform in the primary assay, the original hit (CID 4443990) was selected as probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>.</p></div><div id="ml366.s24"><h3>3.5. Cellular Activity</h3><p>The primary assay and several secondary assays were performed with intact <i>Vibrio cholerae</i> bacteria and compounds were capable of inhibiting an intracellular kinase, LuxO. This cell-based activity suggests that the compounds are able to penetrate the cell and act on an intracellular target. In addition, compounds were tested in a cytotoxicity screen utilizing mammalian HeLa cells without apparent cytotoxicity. An overview of these assays is provided in <a href="#ml366.s8">Section 2.1</a>, and full experimental details can be found in <a href="#ml366.app2">Appendix B</a>. The probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> satisfies the cellular activity criteria specified for this project (refer to <a href="#ml366.s26">Section 4</a>, <a class="figpopup" href="/books/NBK189922/table/ml366.t10/?report=objectonly" target="object" rid-figpopup="figml366t10" rid-ob="figobml366t10">Table 9</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t10"><a href="/books/NBK189922/table/ml366.t10/?report=objectonly" target="object" title="Table 9" class="img_link icnblk_img figpopup" rid-figpopup="figml366t10" rid-ob="figobml366t10"><img class="small-thumb" src="/books/NBK189922/table/ml366.t10/?report=thumb" src-large="/books/NBK189922/table/ml366.t10/?report=previmg" alt="Table 9. Comparison of the performance of ML366 to Project Criteria." /></a><div class="icnblk_cntnt"><h4 id="ml366.t10"><a href="/books/NBK189922/table/ml366.t10/?report=objectonly" target="object" rid-ob="figobml366t10">Table 9</a></h4><p class="float-caption no_bottom_margin">Comparison of the performance of ML366 to Project Criteria. </p></div></div></div><div id="ml366.s25"><h3>3.6. Profiling Assays</h3><p>Because the tentative mode of action for <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is ATPase inhibition, it was also tested at 10 µM in Millipore's KinaseProfiler for potential cross-reactivity towards human kinases. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was remarkably clean against the 59 human kinases tested. The most inhibition seen was at 39% inhibition with CK1γ1 and 29% inhibition of mTOR (See <a class="figpopup" href="/books/NBK189922/table/ml366.t15/?report=objectonly" target="object" rid-figpopup="figml366t15" rid-ob="figobml366t15">Appendix H, Table H1</a>). In addition, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was submitted to Eurofins Panlabs for evaluation in their LeadProfilingScreen to determine possible off-target effects against a broad panel of receptors, ion channels, and transporters. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> had a very clean profile with no binding in most assays and weak activity against Adenosine A3 (38%), Dopamine D<sub>4.2</sub> (36%) and Melatonin MT1 (34%). Data from the kinase profiling assays are available in <a class="figpopup" href="/books/NBK189922/table/ml366.t16/?report=objectonly" target="object" rid-figpopup="figml366t16" rid-ob="figobml366t16">Appendix H, Table H2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t15"><a href="/books/NBK189922/table/ml366.t15/?report=objectonly" target="object" title="Table H1" class="img_link icnblk_img figpopup" rid-figpopup="figml366t15" rid-ob="figobml366t15"><img class="small-thumb" src="/books/NBK189922/table/ml366.t15/?report=thumb" src-large="/books/NBK189922/table/ml366.t15/?report=previmg" alt="Table H1. Human kinase profiling results for ML366." /></a><div class="icnblk_cntnt"><h4 id="ml366.t15"><a href="/books/NBK189922/table/ml366.t15/?report=objectonly" target="object" rid-ob="figobml366t15">Table H1</a></h4><p class="float-caption no_bottom_margin">Human kinase profiling results for ML366. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t16"><a href="/books/NBK189922/table/ml366.t16/?report=objectonly" target="object" title="Table H2" class="img_link icnblk_img figpopup" rid-figpopup="figml366t16" rid-ob="figobml366t16"><img class="small-thumb" src="/books/NBK189922/table/ml366.t16/?report=thumb" src-large="/books/NBK189922/table/ml366.t16/?report=previmg" alt="Table H2. Radioligand binding assay results for ML366." /></a><div class="icnblk_cntnt"><h4 id="ml366.t16"><a href="/books/NBK189922/table/ml366.t16/?report=objectonly" target="object" rid-ob="figobml366t16">Table H2</a></h4><p class="float-caption no_bottom_margin">Radioligand binding assay results for ML366. </p></div></div></div></div><div id="ml366.s26"><h2 id="_ml366_s26_">4. Discussion</h2><p>352,083 unique compounds were screened for activity against the <i>Vibrio cholerae</i> quorum sensing pathway. After validation of activity using purified dry powders and several secondary cell-based assays, CID 4443990 was advanced for chemical optimization and SAR investigation that yielded <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>. An additional LuxO inhibitor scaffold (CID 665390) was separately advanced by the University of Kansas MLPCN Chemistry Center to generate probe <a href="/pcsubstance/?term=ML370[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML370</a>.</p><p>The scaffold consists of a 2-amino-5-aryl-oxadizaole. <a class="figpopup" href="/books/NBK189922/figure/ml366.f11/?report=objectonly" target="object" rid-figpopup="figml366f11" rid-ob="figobml366f11">Figure 9</a> depicts the identified hit CID 4443990 and summarizes the various modifications explored during SAR studies. Two primary diversity points (highlighted in blue and green) were investigated with a collection of 29 synthetically prepared analogs. The SAR evaluation demonstrated that neither location could be modified to increase cellular activity; as a result, the original hit was nominated as probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f11" co-legend-rid="figlgndml366f11"><a href="/books/NBK189922/figure/ml366.f11/?report=objectonly" target="object" title="Figure 9" class="img_link icnblk_img figpopup" rid-figpopup="figml366f11" rid-ob="figobml366f11"><img class="small-thumb" src="/books/NBK189922/bin/ml366f11.gif" src-large="/books/NBK189922/bin/ml366f11.jpg" alt="Figure 9. Summary of Analogs Prepared to Investigate the SAR profile of hit CID 4443990." /></a><div class="icnblk_cntnt" id="figlgndml366f11"><h4 id="ml366.f11"><a href="/books/NBK189922/figure/ml366.f11/?report=objectonly" target="object" rid-ob="figobml366f11">Figure 9</a></h4><p class="float-caption no_bottom_margin">Summary of Analogs Prepared to Investigate the SAR profile of hit CID 4443990. Key SAR findings for each site of diversification are provided in italics. </p></div></div><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> activates the quorum sensing pathway of <i>Vibrio cholerae</i> when present at micromolar concentrations (EC<sub>50</sub> = 6.1 µM). Furthermore, the probe does not appear to be toxic to HeLa control cells and therefore satisfies the desired probe criteria for this project (<a class="figpopup" href="/books/NBK189922/table/ml366.t10/?report=objectonly" target="object" rid-figpopup="figml366t10" rid-ob="figobml366t10">Table 9</a>).</p><div id="ml366.s27"><h3>4.1. Comparison to existing art and how the new probe is an improvement</h3><p>A recently identified series of aza-uracil-containing compounds are the only known, reported inhibitors of <i>V. cholerae</i> LuxO [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. The most potent member of this family, designated Aza-U (<i>cf.</i>
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<a class="figpopup" href="/books/NBK189922/figure/ml366.f4/?report=objectonly" target="object" rid-figpopup="figml366f4" rid-ob="figobml366f4">Figure 3</a>), was synthetically prepared and used as the positive control for all cell-based assays. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is more potent than Aza-U in the primary assay when compared directly (EC<sub>50</sub> = 6.1 µM and >35 µM, respectively). Consistently across all of the assays, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> performed better than Aza-U (<a class="figpopup" href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" rid-figpopup="figml366f7" rid-ob="figobml366f7">Figure 5C</a>, <a class="figpopup" href="/books/NBK189922/figure/ml366.f9/?report=objectonly" target="object" rid-figpopup="figml366f9" rid-ob="figobml366f9">Figure 7B</a>, <a class="figpopup" href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object" rid-figpopup="figml366t11" rid-ob="figobml366t11">Table 10</a> & <a class="figpopup" href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-figpopup="figml366t12" rid-ob="figobml366t12">11</a>). In BH1578, BH1651, and DH231, only the positive control dose of 40 µM induces light production and the lower doses do not generate a consistent dose-dependent response (see <a class="figpopup" href="/books/NBK189922/figure/ml366.f7/?report=objectonly" target="object" rid-figpopup="figml366f7" rid-ob="figobml366f7">Figures 5C</a> & <a class="figpopup" href="/books/NBK189922/figure/ml366.f9/?report=objectonly" target="object" rid-figpopup="figml366f9" rid-ob="figobml366f9">7B</a>). In the WN1103 assay, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is more potent compared to Aza-U (2.1 to 21 µM, respectively, <a class="figpopup" href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-figpopup="figml366t12" rid-ob="figobml366t12">Table 11</a>). In addition to Aza-U, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was compared to the natural QS ligand, CAI-1, as well as two other small molecule CqsS agonists previously reported by our group in late 2012 and the results of this comparison are summarized in <a class="figpopup" href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object" rid-figpopup="figml366t11" rid-ob="figobml366t11">Table 10</a>. It is anticipated that the current LuxO probes <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and <a href="/pcsubstance/?term=ML370[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML370</a> will provide valuable information regarding available binding pockets of <i>V. cholera</i> LuxO and guide the development of the next generation of quorum sensing focused anti-vibrio therapeutics.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t11"><a href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object" title="Table 10" class="img_link icnblk_img figpopup" rid-figpopup="figml366t11" rid-ob="figobml366t11"><img class="small-thumb" src="/books/NBK189922/table/ml366.t11/?report=thumb" src-large="/books/NBK189922/table/ml366.t11/?report=previmg" alt="Table 10. Comparison of Project Probes to Natural Ligand and Prior Art." /></a><div class="icnblk_cntnt"><h4 id="ml366.t11"><a href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object" rid-ob="figobml366t11">Table 10</a></h4><p class="float-caption no_bottom_margin">Comparison of Project Probes to Natural Ligand and Prior Art. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t12"><a href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" title="Table 11" class="img_link icnblk_img figpopup" rid-figpopup="figml366t12" rid-ob="figobml366t12"><img class="small-thumb" src="/books/NBK189922/table/ml366.t12/?report=thumb" src-large="/books/NBK189922/table/ml366.t12/?report=previmg" alt="Table 11. Probe Activation of Quorum Sensing in Vibrio cholerae Mutant Strains." /></a><div class="icnblk_cntnt"><h4 id="ml366.t12"><a href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-ob="figobml366t12">Table 11</a></h4><p class="float-caption no_bottom_margin">Probe Activation of Quorum Sensing in <i>Vibrio cholerae</i> Mutant Strains. ML366 and several analogs were evaluated in alternative <i>V. cholerae</i> mutants to establish possible modes of action. The reported EC<sub>50</sub> values are the average of at least two independent <a href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-ob="figobml366t12">(more...)</a></p></div></div><p>Before the development of these chemical probes, CAI-1, the endogenous ligand of CqsS was the best small molecule available for inhibiting quorum sensing in <i>Vibrio cholera</i>. The long hydrophobic tail of CAI-1 leads to significant micelle formation making it a less attractive chemical tool. All the probes developed in this project (<a class="figpopup" href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object" rid-figpopup="figml366t11" rid-ob="figobml366t11">Table 10</a>) including <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> do not have structural features that promote micelle formation and we expect these probes to have broad utility.</p></div><div id="ml366.s28"><h3>4.2. Mechanism of Action Studies</h3><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was evaluated for its ability to activate the quorum sensing pathways of additional <i>V. cholerae</i> strains (<a class="figpopup" href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-figpopup="figml366t12" rid-ob="figobml366t12">Table 11</a>). Strain BH1651 expresses a constitutively active LuxO<sup>D47E</sup> mutant (PubChem <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651847" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 651847</a>) as described in <a href="#ml366.s11">Section 2.1.3</a>. For this particular bacterial strain, LuxO is locked into an active conformation and thus the signaling processes downstream of LuxO are actively diverted to promote AphA expression. Consequently, HapR and luciferase expression is continuously repressed independent of CqsS or LuxPQ signaling. The ability of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> to promote light production in BH1651 suggests the compound acts upon or downstream of LuxO, consistent with the putative activity of LuxO inhibitors. <i>V. cholerae</i> DH231 and WN1103 are mutant strains lacking CqsS and LuxQ membrane receptors, respectively. If <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> is working downstream of either CqsS or LuxPQ, the DH231 and WN1103 cells should activate light production with compound treatment. This predicted phenotype is precisely what is observed (<a class="figpopup" href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object" rid-figpopup="figml366t12" rid-ob="figobml366t12">Table 11, entries 3-4</a>). This activity profile appears to be conserved across both LuxO inhibitors (<a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and <a href="/pcsubstance/?term=ML370[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML370</a>); QS agonists like CAI-1, <a href="/pcsubstance/?term=ML343[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML343</a> and <a href="/pcsubstance/?term=ML344[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML344</a> activate <i>V. cholerae</i> QS only if the cells express the CqsS receptor. Compared to DMSO, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> significantly decreases LuxO ATPase activity <i>in vitro</i> (<i>cf.</i>
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<a class="figpopup" href="/books/NBK189922/figure/ml366.f9/?report=objectonly" target="object" rid-figpopup="figml366f9" rid-ob="figobml366f9">Figure 7C</a>). This suggests that <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> inhibits LuxO in a similar manner to Aza-U by directly targeting LuxO itself [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>].</p></div><div id="ml366.s29"><h3>4.3. Planned Future Studies</h3><p>In addition to <i>V. cholerae</i>, there are at least six <i>Vibrio</i> species that cause disease in humans and are contracted through contaminated water or ingested during consumption of seafood [<a class="bibr" href="#ml366.r17" rid="ml366.r17">17</a>]. Aza-U inhibits LuxO in multiple <i>Vibrio</i> species, including <i>V. harveyi</i> and <i>V. haemolyticus</i> [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> will be tested against these and multiple vibrios for the ability to shutdown virulence factor production. Combinatorial therapies have proven efficacious in a number of infectious disease treatment regimens and could also be applicable in treating cholera. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> will be tested in combination with several CqsS agonists and the natural CAI-1 ligand. <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and the other probes will also be tested in animal models of cholera. Since LuxO is a kinase, <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was tested against a panel of 60 human kinases representing multiple branches of the kinome to gauge potential host-pathogen specificity (see <a class="figpopup" href="/books/NBK189922/table/ml366.t15/?report=objectonly" target="object" rid-figpopup="figml366t15" rid-ob="figobml366t15">Appendix H, Table H1</a>). Identification and characterization of the binding site(s) occupied by <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> will be undertaken. These studies will include analysis with several LuxO mutants in cells and using <i>in vitro</i> kinase and ATPase assays. Other experiments could include structural efforts. This structural information will undoubtedly be beneficial in the development of additional LuxO inhibitors as potential anti-cholera therapeutics. Co-crystallization of LuxO with the probe is the most attractive possibility for successful crystallization, but protein NMR binding studies are also an option. Other methods to determine probe-protein interaction, albeit with less precision, are biophysical experiments to determine direct binding of the compound to the LuxO protein. Differential scanning fluorimetry (DSF) or thermal shift is a means of detecting binding of a ligand to purified protein. This technique is routinely used in our laboratory and could be applied to LuxO.</p><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> would benefit from additional chemical optimization to improve solubility and murine plasma stability. Also, evaluation of <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> in a panel of <i>in vitro</i> ADME assays and potential optimization of ADME properties to enable <i>in vivo</i> studies would be beneficial. From a structural perspective, investigating additional heteroaromatic rings may be necessary (<a class="figpopup" href="/books/NBK189922/figure/ml366.f12/?report=objectonly" target="object" rid-figpopup="figml366f12" rid-ob="figobml366f12">Figure 10</a>). It is likely that the lipophilic cyclohexyl amide cannot be readily manipulated, but it may be possible to replace the central oxadiazole with more soluble heterocycles such as pyridine or pyrazine. Additional five-membered heterocycles should also be considered. Reduction of the eastern benzodioxane was not tolerated, so bicyclic replacements will be attempted. Substituted quinolines or purines may provide the desired potency and solubility. Following the example of Hilfiker and coworkers [<a class="bibr" href="#ml366.r18" rid="ml366.r18">18</a>], benzomorpholines and benzopiperazines may also be viable alternatives.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml366f12" co-legend-rid="figlgndml366f12"><a href="/books/NBK189922/figure/ml366.f12/?report=objectonly" target="object" title="Figure 10" class="img_link icnblk_img figpopup" rid-figpopup="figml366f12" rid-ob="figobml366f12"><img class="small-thumb" src="/books/NBK189922/bin/ml366f12.gif" src-large="/books/NBK189922/bin/ml366f12.jpg" alt="Figure 10. Possible directions for future SAR investigation of ML366." /></a><div class="icnblk_cntnt" id="figlgndml366f12"><h4 id="ml366.f12"><a href="/books/NBK189922/figure/ml366.f12/?report=objectonly" target="object" rid-ob="figobml366f12">Figure 10</a></h4><p class="float-caption no_bottom_margin">Possible directions for future SAR investigation of ML366. </p></div></div></div></div><div id="ml366.s30"><h2 id="_ml366_s30_">5. References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ml366.r1">Rombel I, North A, Hwang I, Wyman C, Kustu S. The bacterial enhancer-binding protein NtrC as a molecular machine. <span><span class="ref-journal">Cold Spring Harb Symp Quant Biol. </span>1998;<span class="ref-vol">63</span>:157–66.</span> Review. [<a href="https://pubmed.ncbi.nlm.nih.gov/10384279" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10384279</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ml366.r2">Ng WL, Perez L, Cong J, Semmelhack MF, Bassler BL. Broad spectrum pro-quorum sensing molecules as inhibitors of virulence in Vibrios. <span><span class="ref-journal">PLOS Pathog. </span><span class="ref-vol">8</span>(6):e1002767.</span> [<a href="/pmc/articles/PMC3386246/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3386246</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22761573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22761573</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ml366.r3">Dutta NK, Habbu MK. Experimental cholera in infant rabbits: a method for chemotherapeutic investigation. <span><span class="ref-journal">Br J Pharmacol Chemother. </span>1955 Jun;<span class="ref-vol">10</span>(2):153–9.</span> [<a href="/pmc/articles/PMC1509487/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1509487</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14389652" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14389652</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ml366.r4">Aziz KM, Mohsin AK, Hare WK, Phillips RA. Using the rat as a cholera “model” <span><span class="ref-journal">Nature. </span>1968 Nov 23;<span class="ref-vol">220</span>(5169):814–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/5725345" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5725345</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ml366.r5">Klose KE. The suckling mouse model of cholera. <span><span class="ref-journal">Trends Microbiol. </span>2000 Apr;<span class="ref-vol">8</span>(4):189–91.</span> Review. [<a href="https://pubmed.ncbi.nlm.nih.gov/10754579" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10754579</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ml366.r6">Ali M, Lopez AL, You YA, Kim YE, Sah B, Maskery B, Clemens J. The global burden of cholera. <span><span class="ref-journal">Bull World Health Organ. </span>2012 Mar 1;<span class="ref-vol">90</span>(3):209–218A.</span> Epub 2012 Jan 24. [<a href="/pmc/articles/PMC3314202/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3314202</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22461716" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22461716</span></a>] [<a href="http://dx.crossref.org/10.2471/BLT.11.093427" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ml366.r7">Casino P, Rubio V, Marina A. The mechanism of signal transduction by two-component systems. <span><span class="ref-journal">Curr Opin Struct Biol. </span>2010 Dec;<span class="ref-vol">20</span>(6):763–71.</span> Epub 2010 Oct 13. Review. [<a href="https://pubmed.ncbi.nlm.nih.gov/20951027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20951027</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="ml366.r8">Rutherford ST, Bassler BL. Bacterial quorum sensing: Its role in virulence and possibilities for its control. <span><span class="ref-journal">Cold Spring Harb Perspect Med. </span>2012;<span class="ref-vol">2</span>:a012427.</span> [<a href="/pmc/articles/PMC3543102/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3543102</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23125205" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23125205</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="ml366.r9">Miller MB, Skorupski K, Lenz DH, Taylor RK, Bassler BL. Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. <span><span class="ref-journal">Cell. </span>2002 Aug 9;<span class="ref-vol">110</span>(3):303–14.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12176318" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12176318</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="ml366.r10">Higgins DA, Pomianek ME, Kraml CM, Taylor RK, Semmelhack MF, Bassler BL. The major Vibrio cholerae autoinducer and its role in virulence factor production. <span><span class="ref-journal">Nature. </span>2007 Dec 6;<span class="ref-vol">450</span>(7171):883–6.</span> Epub 2007 Nov 14. [<a href="https://pubmed.ncbi.nlm.nih.gov/18004304" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18004304</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="ml366.r11">Wei Y, Ng WL, Cong J, Bassler BL. Ligand and antagonist driven regulation of the Vibrio cholerae quorum sensing receptor CqsS. <span><span class="ref-journal">Mol Microbiol. </span>2012 Mar;<span class="ref-vol">83</span>(6):1095–108.</span> Epub 2012 Feb 14. [<a href="/pmc/articles/PMC3310172/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3310172</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22295878" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22295878</span></a>] [<a href="http://dx.crossref.org/10.1111/j.1365-2958.2012.07992.x" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="ml366.r12">Lenz DH, Mok KC, Linney BN, Kulkarni RV, Wingreen NS, Bassler BL. The small chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. <span><span class="ref-journal">Cell. </span>2004;<span class="ref-vol">118</span>:69–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15242645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15242645</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="ml366.r13">Studholme DJ, Dixon R. Domain architectures of sigma54-dependent transcriptional activators. <span><span class="ref-journal">J Bacteriol. </span>2003 Mar;<span class="ref-vol">185</span>(6):1757–67.</span> Review. [<a href="/pmc/articles/PMC150144/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC150144</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12618438" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12618438</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="ml366.r14">Zhu J, Mekalanos JJ. Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. <span><span class="ref-journal">Dev Cell. </span>2003 Oct;<span class="ref-vol">5</span>(4):647–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14536065" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14536065</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="ml366.r15">Ng WL, Perez LJ, Wei Y, Kraml C, Semmelhack MF, Bassler BL. Signal production and detection specificity in Vibrio CqsA/CqsS quorum sensing systems. <span><span class="ref-journal">Mol Microbiol. </span>2011 Mar;<span class="ref-vol">79</span>(6):1407–17.</span> Epub 2011 Jan 26. [<a href="/pmc/articles/PMC3285556/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3285556</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21219472" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21219472</span></a>] [<a href="http://dx.crossref.org/10.1111/j.1365-958.2011.07548.x" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="ml366.r16">Svenningsen SL, Waters CM, Bassler BL. A negative feedback loop involving small RNAs accelerates <em>Vibrio cholerae</em>'s transition out of quorum-sensing mode. <span><span class="ref-journal">Genes Dev. </span>2008;<span class="ref-vol">22</span>:226–238.</span> [<a href="/pmc/articles/PMC2192756/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2192756</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18198339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18198339</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="ml366.r17">Shinoda S, Miyoshi SI. Proteases produced by vibrios. <span><span class="ref-journal">Biocontrol Science. </span>2011;<span class="ref-vol">16</span>(1):1–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21467624" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21467624</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="ml366.r18">Hilfiker MA, Wang N, Hou X, Du Z, Pullen MA, Nord M, Nagilla R, Fries HE, Wu CW, Sulpizio AC, Jaworski JP, Morrow D, Edwards RM, Jin J. Discovery of novel aminothiadiazole amides as selective EP(3) receptor antagonists. <span><span class="ref-journal">Bioorg Med Chem Lett. </span>2009 Aug 1;<span class="ref-vol">19</span>(15):4292–5.</span> Epub 2009 May 27. [<a href="https://pubmed.ncbi.nlm.nih.gov/19487124" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19487124</span></a>] [<a href="http://dx.crossref.org/10.1016/j.bmcl.2009.05.074" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl></dl></div><div id="ml366.app1"><h2 id="_ml366_app1_">Appendix A. Assay Summary Table</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t13"><a href="/books/NBK189922/table/ml366.t13/?report=objectonly" target="object" title="Table A1" class="img_link icnblk_img figpopup" rid-figpopup="figml366t13" rid-ob="figobml366t13"><img class="small-thumb" src="/books/NBK189922/table/ml366.t13/?report=thumb" src-large="/books/NBK189922/table/ml366.t13/?report=previmg" alt="Table A1. Summary of Completed Assays and AIDs." /></a><div class="icnblk_cntnt"><h4 id="ml366.t13"><a href="/books/NBK189922/table/ml366.t13/?report=objectonly" target="object" rid-ob="figobml366t13">Table A1</a></h4><p class="float-caption no_bottom_margin">Summary of Completed Assays and AIDs. </p></div></div></div><div id="ml366.app2"><h2 id="_ml366_app2_">Appendix B. Detailed Assay Protocols</h2><div id="ml366.s31"><h3><i>V. cholerae</i> BH1578 primary bioluminescence assay (2132-01) (AID 588346, AID 602243, AID 624270, AID 651854, AID 651809, AID 651816, AID 652239, AID 686929)</h3><h4><span class="title">Materials and Reagents</span></h4><ul><li class="half_rhythm"><div>Bacterial strain: BH1578 (<i>V. cholerae</i> Δ<i>cqsA</i> Δ<i>luxS</i> carrying pBB1 cosmid, which contains the <i>V. harveyi luxCDABE</i> luciferase operon)</div></li><li class="half_rhythm"><div>LB Medium: Dissolve in 10 g/L Tryptone, 5 g/L Yeast Extract, and 10 g/L NaCl in distilled water, autoclave, store at room temperature</div></li><li class="half_rhythm"><div>Tetracycline (10 mg/mL): Dissolve 10 mg tetracycline in 1 mL 100% ethanol, store at -20 °C, protect from light.</div></li><li class="half_rhythm"><div>LB/tet: add 1 mL tetracycline (10 mg/mL) to 1 L of LB medium. Final concentration of tetracycline is 10 µg/mL. Make it fresh for every use.</div></li><li class="half_rhythm"><div>CAI-1 stock: Dissolve CAI-1 in DMSO to 50 mM (10.7 mg/mL), store at -20 °C</div></li></ul><h4><span class="title">Procedure</span></h4><ol><li class="half_rhythm"><div>Grow up BH1578 reporter strain in 50 mL LB/Tet at 30 °C for >16 hours with shaking (200 rpm). The final OD<sub>600</sub> of each culture should be > 3.0.</div></li><li class="half_rhythm"><div>Adjust culture to OD<sub>600</sub> = 0.3, mix well. (Note: a low speed centrifugation (200 rpm for 1 min) removed most biofilm aggregates).</div></li><li class="half_rhythm"><div>Add 20 µL LB/tet per well with Thermo Combi MultiDrop fluid dispenser into a 384 well plate. (Greiner black, clear bottom plates were used for HTS while Corning 8867BC white opaque 384 plates were used for subsequent assays).</div></li><li class="half_rhythm"><div>Pin transfer 100 nL compound or 1 µM CAI-1 as positive control per well from compound source plate to assay plate (pinning volume was 150 nL for the primary HTS).</div></li><li class="half_rhythm"><div>Dispense 10 µL of diluted culture into each well of a 384 well plate.</div></li><li class="half_rhythm"><div>Incubate the plates at 30 °C without shaking for 6 hours.</div></li><li class="half_rhythm"><div>Measure bioluminescence (Lum(384)) and OD<sub>600</sub> in a Perkin-Elmer Envision Multilabel Reader</div></li></ol><p>For dose retests, compounds were arrayed so that 2 rows of DMSO were located between each test compound. This minimized any signal from a neighboring well yielding a false positive due to an extremely high bioluminescence signal.</p></div><div id="ml366.s32"><h3><i>V. cholerae</i> BH1651 secondary LuxO inhibitor bioluminescence assay (2132-03) (AID 624254, AID 624269, AID 651847, AID 652289)</h3><h4><span class="title">Materials and Reagents</span></h4><ul><li class="half_rhythm"><div>Bacterial strain: BH1651 (<i>V. cholerae luxO<sup>D47E</sup></i> carrying pBB1 cosmid, which contains the <i>V. harveyi luxCDABE</i> luciferase operon)</div></li><li class="half_rhythm"><div>LB Medium: Dissolve in 10 g/L Tryptone, 5 g/L Yeast Extract, and 10 g/L NaCl in distilled water, autoclave, store at room temperature</div></li><li class="half_rhythm"><div>Tetracycline (10 mg/mL): Dissolve 10 mg tetracycline in 1 mL 100% ethanol, store at -20 °C, protect from light.</div></li><li class="half_rhythm"><div>LB/tet: add 1 mL tetracycline (10 mg/mL) to 1 L of LB medium. Final concentration of tetracycline is 10 µg/mL. Make it fresh for every use.</div></li></ul><h4><span class="title">Procedure</span></h4><ol><li class="half_rhythm"><div>Grow up BH1651 reporter strain in 50 mL LB/Tet at 30 °C for >16 hours with shaking (200 rpm). The final OD<sub>600</sub> of each culture should be > 3.0.</div></li><li class="half_rhythm"><div>Adjust culture to OD<sub>600</sub> = 0.3, mix well. (Note: a low speed centrifugation (200 rpm for 1 min) removed most biofilm aggregates).</div></li><li class="half_rhythm"><div>Add 20 µL LB/tet per well with Thermo Combi MultiDrop fluid dispenser into a 384 well plate. (Greiner black, clear bottom plates were used for HTS while Corning 8867BC white opaque 384 plates were used for subsequent assays).</div></li><li class="half_rhythm"><div>Pin transfer 100 nL compound per well from compound source plate to assay plate.</div></li><li class="half_rhythm"><div>Dispense 10 µL of diluted culture into each well of a 384 well plate.</div></li><li class="half_rhythm"><div>Incubate the plates at 30 °C without shaking for 6 hours.</div></li><li class="half_rhythm"><div>Measure bioluminescence (Lum(384)) and OD<sub>600</sub> in a Perkin-Elmer Envision Multilabel Reader</div></li></ol><p>For dose retests, compounds were arrayed so that 2 rows of DMSO were located between each test compound. This minimized any signal from a neighboring well yielding a false positive due to an extremely high bioluminescence signal.</p></div><div id="ml366.s33"><h3><i>V. cholerae</i> DH231 secondary sensor mechanism bioluminescence assay (2132-04) (AID 624281, AID 651808, AID 686931)</h3><h4><span class="title">Materials and Reagents</span></h4><ul><li class="half_rhythm"><div>Bacterial strain: DH231 (<i>V. cholerae</i> Δ<i>cqsS</i> Δ<i>luxS</i> carrying pBB1 cosmid, which contains the <i>V. harveyi luxCDABE</i> luciferase operon)</div></li><li class="half_rhythm"><div>LB Medium: Dissolve in 10 g/L Tryptone, 5 g/L Yeast Extract, and 10 g/L NaCl in distilled water, autoclave, store at room temperature</div></li><li class="half_rhythm"><div>Tetracycline (10 mg/mL): Dissolve 10 mg tetracycline in 1 mL 100% ethanol, store at -20 °C, protect from light.</div></li><li class="half_rhythm"><div>LB/tet: add 1 mL tetracycline (10 mg/mL) to 1 L of LB medium. Final concentration of tetracycline is 10 µg/mL. Make it fresh for every use.</div></li><li class="half_rhythm"><div>CAI-1 stock: Dissolve CAI-1 in DMSO to 50 mM (10.7 mg/mL), store at -20 °C</div></li></ul><h4><span class="title">Procedure</span></h4><ol><li class="half_rhythm"><div>Grow up reporter strain in 50 mL LB/Tet at 30 °C for >16 hours with shaking (200 rpm). The final OD<sub>600</sub> of each culture should be > 3.0.</div></li><li class="half_rhythm"><div>Adjust culture to OD<sub>600</sub> = 0.3, mix well. (Note: a low speed centrifugation (200 rpm for 1 min) removed most biofilm aggregates).</div></li><li class="half_rhythm"><div>Add 20 µL LB/tet per well with Thermo Combi MultiDrop fluid dispenser into a 384 well plate. (Corning 8867BC white opaque 384 plates were used).</div></li><li class="half_rhythm"><div>Pin transfer 100 nL compound per well or 1 µM CAI-1 as positive control from compound source plate to assay plate.</div></li><li class="half_rhythm"><div>Dispense 10 µL of diluted culture into each well of a 384 well plate.</div></li><li class="half_rhythm"><div>Incubate the plates at 30 °C without shaking for 6 hours.</div></li><li class="half_rhythm"><div>Measure bioluminescence (Lum(384)) and OD<sub>600</sub> in a Perkin-Elmer Envision Multilabel Reader</div></li></ol><p>For dose retests, compounds were arrayed so that 2 rows of DMSO were located between each test compound. This minimized any signal from a neighboring well yielding a false positive due to an extremely high bioluminescence signal.</p></div><div id="ml366.s34"><h3><i>V. cholerae</i> WN1103 Secondary sensor mechanism bioluminescence assay (2132-05) (AID 624275, AID 651841, AID 686930)</h3><h4><span class="title">Materials and Reagents</span></h4><ul><li class="half_rhythm"><div>Bacterial strain: WN1103 (<i>V. cholerae</i> Δ<i>cqsA</i> Δ<i>luxQ</i> carrying pBB1 cosmid, which contains the <i>V. harveyi luxCDABE</i> luciferase operon)</div></li><li class="half_rhythm"><div>LB Medium: Dissolve in 10 g/L Tryptone, 5 g/L Yeast Extract, and 10 g/L NaCl in distilled water, autoclave, store at room temperature</div></li><li class="half_rhythm"><div>Tetracycline (10 mg/mL): Dissolve 10 mg tetracycline in 1 mL 100% ethanol, store at -20 °C, protect from light.</div></li><li class="half_rhythm"><div>LB/tet: add 1 mL tetracycline (10 mg/mL) to 1 L of LB medium. Final concentration of tetracycline is 10 µg/mL. Make it fresh for every use.</div></li><li class="half_rhythm"><div>CAI-1 stock: Dissolve CAI-1 in DMSO to 50 mM (10.7 mg/mL), store at -20 °C</div></li></ul><h4><span class="title">Procedure</span></h4><ol><li class="half_rhythm"><div>Grow up reporter strain in 50 mL LB/Tet at 30 °C for >16 hours with shaking (200 rpm). The final OD<sub>600</sub> of each culture should be > 3.0.</div></li><li class="half_rhythm"><div>Adjust culture to OD<sub>600</sub> = 0.3, mix well. (Note: a low speed centrifugation (200 rpm for 1 min) removed most biofilm aggregates).</div></li><li class="half_rhythm"><div>Add 20 µL LB/tet per well with Thermo Combi MultiDrop fluid dispenser into a 384 well plate. (Corning white opaque 8867BC 384 plates were used).</div></li><li class="half_rhythm"><div>Pin transfer 100 nL compound or 1 µM CAI-1 as positive control per well from compound source plate to assay plate.</div></li><li class="half_rhythm"><div>Dispense 10 µL of diluted culture into each well of a 384 well plate.</div></li><li class="half_rhythm"><div>Incubate the plates at 30 °C without shaking for 6 hours.</div></li><li class="half_rhythm"><div>Measure bioluminescence (Lum(384)) and OD<sub>600</sub> in a Perkin-Elmer Envision Multilabel Reader</div></li></ol><p>For dose retests, compounds were arrayed so that 2 rows of DMSO were located between each test compound. This minimized any signal from a neighboring well yielding a false positive due to an extremely high bioluminescence signal.</p></div><div id="ml366.s35"><h3><i>V. cholerae</i> SLS353 secondary qrr4:GFP fluorescence reporter assay (2132-06) (AID 652219, AID 686942)</h3><h4><span class="title">Materials and Reagents</span></h4><ul><li class="half_rhythm"><div>Bacterial strain: SLS353 (<i>V. cholerae luxO<sup>D47E</sup></i> carrying qrr4:GFP plasmid)</div></li><li class="half_rhythm"><div>LB Medium: Dissolve in 10 g/L Tryptone, 5 g/L Yeast Extract, and 10 g/L NaCl in distilled water, autoclave, store at room temperature</div></li><li class="half_rhythm"><div>Kanamycin (100 mg/mL): Dissolve 100 mg kanamycin in 1 mL water, store at -20 °C</div></li><li class="half_rhythm"><div>LB/Kan: add 1 mL Kanamycin (100 mg/mL) to 1 L of LB medium. Final concentration of Kanamycin is 100 µg/mL. Make it fresh for every use.</div></li></ul><h4><span class="title">Procedure</span></h4><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>8.</dt><dd><p class="no_top_margin">Grow up strain in 50 mL LB/Kan at 30 °C for >16 hours with shaking (200 rpm). The final OD<sub>600</sub> of each culture should be > 3.0.</p></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><p class="no_top_margin">Adjust culture to OD<sub>600</sub> = 0.3, mix well. (Note: a low speed centrifugation (200 rpm for 1 min) removed most biofilm aggregates).</p></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><p class="no_top_margin">Add 20 µL LB/Kan per well with Thermo Combi MultiDrop fluid dispenser into a 384 well plate. (Corning black opaque 384 plates were used).</p></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><p class="no_top_margin">Pin transfer 100 nL compound per well from compound source plate to assay plate.</p></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><p class="no_top_margin">Dispense 10 µL of diluted SLS353 culture into each well of a 384 well plate.</p></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><p class="no_top_margin">Incubate the plates at 30 °C without shaking for 16 hours.</p></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><p class="no_top_margin">Measure GFP fluorescence in a Perkin-Elmer Envision Multilabel Reader</p></dd></dl></dl></div><div id="ml366.s36"><h3>LuxO i<i>n vitro</i> ATPase assay (AID No. 686936)</h3><div id="ml366.s37"><h4>Procedure</h4><p>A modified coupled-enzyme assay measured the rate of ATP hydrolysis by LuxO<i><sup>D47E</sup></i> [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. Briefly, ADP released from ATP by LuxO<i><sup>D47E</sup></i> is reacted with phosphoenolpyruvate (PEP) to form pyruvate using pyruvate kinase (PK). Pyruvate is reacted with NADH to form NAD and lactate using lactate dehydrogenase (LDH). The rate of NAD production is followed at 340 nm using a spectrophotometer. ATP hydrolysis rates were inferred from the absorbance change observed (ε<sub>NADH,340</sub> -ε-<sub>NAD,340</sub> = 6220 M<sup>-1</sup> cm<sup>-1</sup> for NADH) [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>]. The rates of ATP hydrolysis by LuxO<i><sup>D47E</sup></i> were measured in reactions containing 100 mM Sodium phosphate buffer pH 7.4, 5 mM MgCl<sub>2</sub>, 0.2 mM NADH, 1 mM PEP, 5–20 units of PK/LDH mix (Sigma), and 10 mM LuxO<i><sup>D47E</sup></i>. ATP and inhibitors were added to the reactions at indicated concentrations. The rate of ATP hydrolysis was monitored for 5 minutes. Data were fitted using GraphPad Prism to obtain the kinetic parameters. Percent ATPase inhibition was calculated.</p></div></div><div id="ml366.s38"><h3>Data Analysis</h3><p>For the primary screen and other assays, negative-control (NC) wells and positive-control (PC) wells were included on every plate. The raw signals of the plate wells were normalized using the ‘Stimulators Minus Neutral Controls’ or the ‘Neutral Controls’ method (when no positive control was available) in GeneData Screener Assay Analyzer (v7.0.3 & v10.0.2). The median raw signal of the intra-plate NC wells was set to a normalized activity value of 0, while the median raw signal of the intra-plate PC wells was set to a normalized activity value of 100. Experimental wells were scaled to this range, resulting in an activity score representing the percent change in signal relative to the intra-plate controls. The mean of the replicate percent activities were presented as the final ‘PubChem Activity Score’. The ‘PubChem Activity Outcome’ class was assigned as described below, based on an activity threshold of 70%:</p><ul><li class="half_rhythm"><div>Activity_Outcome = 1 (inactive), less than half of the replicates fell outside the threshold.</div></li><li class="half_rhythm"><div>Activity_Outcome = 2 (active), all of the replicates fell outside the threshold, OR at least half of the replicates fell outside the threshold AND the ‘PubChem Activity Score’ fell outside the threshold.</div></li><li class="half_rhythm"><div>Activity_Outcome = 3 (inconclusive), at least half of the replicates fell outside the threshold AND the ‘PubChem Activity Score did not fall outside the threshold.</div></li></ul></div></div><div id="ml366.app3"><h2 id="_ml366_app3_">Appendix C. Experimental Procedures for the Synthesis of Probe ML366</h2><p><b>General Details.</b> All reagents and solvents were purchased from commercial vendors and used as received. NMR spectra were recorded on a Bruker 300 MHz or Varian UNITY INOVA 500 MHz spectrometer as indicated. Proton and carbon chemical shifts are reported in parts per million (ppm; δ) relative to tetramethylsilane internal standard (<sup>1</sup>H δ 0.0, <sup>13</sup>C δ 0.0) or residual DMSO solvent (<sup>1</sup>H δ 2.50, <sup>13</sup>C δ 39.52). NMR data are reported as follows: chemical shifts, multiplicity (obs = obscured, app = apparent, br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet); coupling constant(s) in Hz; integration. Unless otherwise indicated, NMR data were collected at 25 °C. Flash chromatography was performed using 40-60 um Silica Gel (60 Å mesh) on a Teledyne Isco Combiflash Rf system. Tandem liquid chromatography/mass spectrometry (LCMS) was performed on a Waters 2795 separations module and Waters 3100 mass detector. Analytical thin layer chromatography (TLC) was performed on EM Reagent 0.25 mm silica gel 60-F plates. Visualization was accomplished with UV light and aqueous potassium permanganate (KMnO<sub>4</sub>) stain followed by heating. High-resolution mass spectra were obtained on an Agilent 1290 Infinity separations module and 6230 time-of-flight (TOF) mass detector operating in ESI+ mode. Compound purity and identity were determined by UPLC-MS (Waters, Milford, MA). Purity was measured by UV absorbance at 210 nm. Identity was determined on a SQ mass spectrometer by positive electrospray ionization. Mobile Phase A consisted of either 0.1% ammonium hydroxide or 0.1% trifluoroacetic acid in water, while mobile Phase B consisted of the same additives in acetonitrile. The gradient ran from 5% to 95% mobile Phase B over 0.8 minutes at 0.45 mL/min. An Acquity BEH C18, 1.7 um, 1.0 × 50 mm column was used with column temperature maintained at 65 °C. Compounds were dissolved in DMSO at a nominal concentration of 1 mg/mL, and 0.25 µL of this solution was injected.</p><div id="ml366.f13" class="figure"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20ml366f13&p=BOOKS&id=189922_ml366f13.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f13.jpg" alt="Image ml366f13" class="tileshop" title="Click on image to zoom" /></a></div></div><p><b><i>N</i>-(5-(2,3-dihydrobenzo[b][<a class="bibr" href="#ml366.r1" rid="ml366.r1">1</a>,<a class="bibr" href="#ml366.r4" rid="ml366.r4">4</a>]dioxin-6-yl)-1,3,4-oxadiazol-2-yl)cyclohexanecarboxamide (7)</b>: To a solution of amine <b>6</b> (100.0 mg, 0.46 mmol, purchased from Enamine Cat. No. EN300-69427), 4-<i>N</i>,<i>N</i>-dimethylaminopyridine (5.6 mg, 0.046 mmol, 0.1 equiv), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (175 mg, 0.91 mmol, 2.0 equiv) in <i>N</i>,<i>N</i>-dimethylformamide (1.8 mL) was added diisopropylethylamine (0.16 mL, 0.91 mmol, 2.0 equiv) and cyclohexanecarboxylic acid (70 µL, 0.56 mmol, 1.2 equiv). The resulting solution was stirred at room temperature for 72 hours before being diluted with water (5 mL). The precipitated solids were collected by filtration, washed with additional water (10 mL) and dried under vacuum. Recrystallization from ethanol afforded pure product (65.3 mg, 44%). <b><sup>1</sup>H NMR (500 MHz, d<sub>6</sub>-DMSO):</b> δ 11.59 (s, 1H), 7.40–7.36 (m, 1H), 7.34–7.31 (m, 1H), 7.07–7.03 (m, 1H), 4.32 (m, 4H), 2.45 (obs. m, 1H), 1.87–1.81 (m, 2H), 1.77–1.71 (m, 2H), 1.66–1.61 (m, 1H), 1.43–1.33 (m, 2H), 1.30–1.17 (m, 3H); <b><sup>13</sup>C NMR (125 MHz, d<sub>6</sub>-DMSO):</b> δ 173.6, 160.2, 157.2, 146.4, 143.8, 119.5, 118.2, 116.4, 114.5, 64.42, 64.1, 43.9, 28.7, 25.3, 25.0; <b>MS</b> (ESI<sup>+</sup>): 330 (M+H); <b>HRMS:</b> calculated for C<sub>17</sub>H<sub>20</sub>N<sub>3</sub>O<sub>4</sub> [M+H] 330.1448, found 330.1449</p></div><div id="ml366.app4"><h2 id="_ml366_app4_">Appendix D. Experimental Procedure for Additional Analytical Assays</h2><p><b>Solubility</b>. Solubility was determined in phosphate buffered saline (PBS) pH 7.4 with 1% DMSO. Each compound was prepared in triplicate at 100 µM in both 100% DMSO and PBS with 1% DMSO. Compounds were allowed to equilibrate at room temperature with a 350 rpm orbital shake for 18 hours. After equilibration, samples were analyzed by UPLC-MS (Waters, Milford, MA) with compounds detected by SIR detection on a single quadrupole mass spectrometer. The DMSO samples were used to create a two-point calibration curve to which the response in PBS was fit. Solubility in LB media was determined using this method, substituting LB media for DMSO.</p><p><b>PBS Stability</b>. Stability was determined in the presence of PBS pH 7.4 with 1% DMSO. Each compound was prepared in triplicate at 1 µM on six separate plates and allowed to equilibrate at room temperature with a 350-rpm orbital shake for 48 hours. One plate was removed at each time point (0, 2, 4, 8, 24, and 48 hours). An aliquot was removed from each well and analyzed by UPLC-MS (Waters, Milford, MA) with compounds detected by SIR detection on a single quadrupole mass spectrometer. Additionally, to the remaining material at each time point, methanol was added to force dissolution of compound (to test for recovery of compound). An aliquot of this was also analyzed by UPLC-MS.</p><p><b>GSH Stability.</b> Stability was determined in the presence of PBS pH 7.4 µM and 50 µM glutathione with 1% DMSO. Each compound was prepared in duplicate at 1 µM on six separate plates and allowed to equilibrate at room temperature with a 350-rpm orbital shake for 6 hours. One plate was removed at each time point (0, 0.5, 1, 2, 4, and 6 hours). An aliquot was removed from each well and analyzed by UPLC-MS (Waters, Milford, MA) with compounds detected by SIR detection on a single quadrupole mass spectrometer. Additionally, to the remaining material at each time point, methanol was added to force dissolution of compound (to test for recovery of compound). An aliquot of this was also analyzed by UPLC-MS.</p><p><b>Plasma Protein Binding</b>. Plasma protein binding was determined by equilibrium dialysis using the Rapid Equilibrium Dialysis (RED) device (Pierce Biotechnology, Rockford, IL) for both human and mouse plasma. Each compound was prepared in duplicate at 5 µM in plasma (0.95% acetonitrile, 0.05% DMSO) and added to one side of the membrane (200 µL) with PBS pH 7.4 added to the other side (350 µL). Compounds were incubated at 37 ºC for 5 hours with a 250-rpm orbital shake. After incubation, samples were analyzed by UPLC-MS (Waters, Milford, MA) with compounds detected by SIR detection on a single quadrupole mass spectrometer.</p><p><b>Plasma Stability</b>. Plasma stability was determined at 37 ºC at 5 hours in both human and mouse plasma. Each compound was prepared in duplicate at 5 µM in plasma diluted 50/50 (v/v) with PBS pH 7.4 (0.95% acetonitrile, 0.05% DMSO). Compounds were incubated at 37 ºC for 5 hours with a 250-rpm orbital shake with time points taken at 0 hours and 5 hours. Samples were analyzed by UPLC-MS (Waters, Milford, MA) with compounds detected by SIR detection on a single quadrupole mass spectrometer.</p><p><b>Microsomal Stability</b>. Microsomal stability was determined by measuring degradation of the compound over 1 hour in human and/or mouse liver microsomes (Xenotech LLC, Lenexa, KS). Each compound was prepared in duplicate and added to a microsomal solution in PBS pH 7.4 so that the final concentration was 1 µM compound, 0.3 mg/mL microsomes, 0.5 mM NADPH and 1% DMSO. Compounds were incubated at 37 ºC for 1 hour with 250 rpm orbital shake with time points taken at 0 hours and 1 hour. Samples were analyzed by UHPLC-MS (Agilent, Santa Clara, CA) with compounds detected on a time-of-flight mass spectrometer and analyzed using Find By Formula.</p></div><div id="ml366.app5"><h2 id="_ml366_app5_">Appendix E. Chemical Characterization Data of Probe</h2><div id="ml366.f14" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(500%20MHz%2C%20d6-DMSO)%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f14.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f14.jpg" alt="1H NMR Spectrum (500 MHz, d6-DMSO) of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (500 MHz, d<sub>6</sub>-DMSO) of Probe ML366</span></h3></div><div id="ml366.f15" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=13C%20NMR%20Spectrum%20(125%20MHz%2C%20d6-DMSO)%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f15.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f15.jpg" alt="13C NMR Spectrum (125 MHz, d6-DMSO) of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>13</sup>C NMR Spectrum (125 MHz, d<sub>6</sub>-DMSO) of Probe ML366</span></h3></div><div id="ml366.f16" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f16.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f16.jpg" alt="UPLC-MS Chromatogram of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Probe ML366</span></h3></div></div><div id="ml366.app6"><h2 id="_ml366_app6_">Appendix F. Prior Art Search</h2><p>Investigation into relevant prior art entailed searching the following databases: SciFinder, Reaxys, PubChem, PubMed, US Patent and Trademark Office (USPTO PatFT and AppFT), World Intellectual Property Organization (WIPO), and Thomson Reuters Integrity. The search terms applied and hit statistics are provided in <a class="figpopup" href="/books/NBK189922/table/ml366.t14/?report=objectonly" target="object" rid-figpopup="figml366t14" rid-ob="figobml366t14">Table A2</a>. As indicated below, abstracts were obtained for the references returned and were analyzed for relevance to the current project. The searches were originally performed on May 9, 2011. Searches were performed again and updated on April 2, 2013.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t14"><a href="/books/NBK189922/table/ml366.t14/?report=objectonly" target="object" title="Table A2" class="img_link icnblk_img figpopup" rid-figpopup="figml366t14" rid-ob="figobml366t14"><img class="small-thumb" src="/books/NBK189922/table/ml366.t14/?report=thumb" src-large="/books/NBK189922/table/ml366.t14/?report=previmg" alt="Table A2. Search Strings and Databases Employed in Prior Art Search." /></a><div class="icnblk_cntnt"><h4 id="ml366.t14"><a href="/books/NBK189922/table/ml366.t14/?report=objectonly" target="object" rid-ob="figobml366t14">Table A2</a></h4><p class="float-caption no_bottom_margin">Search Strings and Databases Employed in Prior Art Search. </p></div></div></div><div id="ml366.app7"><h2 id="_ml366_app7_">Appendix G. Chemical Characterization Data for All Analogs of ML366</h2><div id="ml366.f17" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%205111732.&p=BOOKS&id=189922_ml366f17.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f17.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 5111732." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 5111732</span></h3></div><div id="ml366.f18" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205111732.&p=BOOKS&id=189922_ml366f18.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f18.jpg" alt="UPLC-MS Chromatogram of Analog CID 5111732." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5111732</span></h3><div class="caption"><p>MW = 301.34</p></div></div><div id="ml366.f19" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%205084468.&p=BOOKS&id=189922_ml366f19.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f19.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 5084468." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 5084468</span></h3></div><div id="ml366.f20" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205084468.&p=BOOKS&id=189922_ml366f20.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f20.jpg" alt="UPLC-MS Chromatogram of Analog CID 5084468." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5084468</span></h3><div class="caption"><p>MW = 301.34</p></div></div><div id="ml366.f21" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%203474144.&p=BOOKS&id=189922_ml366f21.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f21.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 3474144." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 3474144</span></h3></div><div id="ml366.f22" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%203474144.&p=BOOKS&id=189922_ml366f22.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f22.jpg" alt="UPLC-MS Chromatogram of Analog CID 3474144." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 3474144</span></h3><div class="caption"><p>MW = 301.34</p></div></div><div id="ml366.f23" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%204160355.&p=BOOKS&id=189922_ml366f23.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f23.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 4160355." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 4160355</span></h3></div><div id="ml366.f24" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%204160355.&p=BOOKS&id=189922_ml366f24.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f24.jpg" alt="UPLC-MS Chromatogram of Analog CID 4160355." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 4160355</span></h3><div class="caption"><p>MW = 305.76</p></div></div><div id="ml366.f25" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2016854334.&p=BOOKS&id=189922_ml366f25.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f25.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 16854334." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 16854334</span></h3></div><div id="ml366.f26" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2016854334.&p=BOOKS&id=189922_ml366f26.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f26.jpg" alt="UPLC-MS Chromatogram of Analog CID 16854334." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 16854334</span></h3><div class="caption"><p>MW = 305.76</p></div></div><div id="ml366.f27" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%205170103.&p=BOOKS&id=189922_ml366f27.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f27.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 5170103." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 5170103</span></h3></div><div id="ml366.f28" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205170103.&p=BOOKS&id=189922_ml366f28.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f28.jpg" alt="UPLC-MS Chromatogram of Analog CID 5170103." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5170103</span></h3><div class="caption"><p>MW = 305.76</p></div></div><div id="ml366.f29" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%207158403.&p=BOOKS&id=189922_ml366f29.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f29.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 7158403." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 7158403</span></h3></div><div id="ml366.f30" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%207158403.&p=BOOKS&id=189922_ml366f30.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f30.jpg" alt="UPLC-MS Chromatogram of Analog CID 7158403." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 7158403</span></h3><div class="caption"><p>MW = 272.30</p></div></div><div id="ml366.f31" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701498.&p=BOOKS&id=189922_ml366f31.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f31.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701498." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701498</span></h3></div><div id="ml366.f32" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701498.&p=BOOKS&id=189922_ml366f32.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f32.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701498." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701498</span></h3><div class="caption"><p>MW = 263.34</p></div></div><div id="ml366.f33" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%204420019.&p=BOOKS&id=189922_ml366f33.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f33.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 4420019." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 4420019</span></h3></div><div id="ml366.f34" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%204420019.&p=BOOKS&id=189922_ml366f34.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f34.jpg" alt="UPLC-MS Chromatogram of Analog CID 4420019." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 4420019</span></h3><div class="caption"><p>MW = 287.27</p></div></div><div id="ml366.f35" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525024.&p=BOOKS&id=189922_ml366f35.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f35.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525024</span></h3></div><div id="ml366.f36" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525024.&p=BOOKS&id=189922_ml366f36.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f36.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525024</span></h3><div class="caption"><p>MW = 301.30</p></div></div><div id="ml366.f37" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525030.&p=BOOKS&id=189922_ml366f37.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f37.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525030." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525030</span></h3></div><div id="ml366.f38" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525030.&p=BOOKS&id=189922_ml366f38.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f38.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525030." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525030</span></h3><div class="caption"><p>MW = 315.32</p></div></div><div id="ml366.f39" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525038.&p=BOOKS&id=189922_ml366f39.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f39.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525038." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525038</span></h3></div><div id="ml366.f40" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525038.&p=BOOKS&id=189922_ml366f40.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f40.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525038." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525038</span></h3><div class="caption"><p>MW = 343.38</p></div></div><div id="ml366.f41" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525031.&p=BOOKS&id=189922_ml366f41.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f41.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525031." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525031</span></h3></div><div id="ml366.f42" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=LCMS%20Chromatogram%20of%20Analog%20CID%2057525031.&p=BOOKS&id=189922_ml366f42.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f42.jpg" alt="LCMS Chromatogram of Analog CID 57525031." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">LCMS Chromatogram of Analog CID 57525031</span></h3><div class="caption"><p>MW = 331.32</p></div></div><div id="ml366.f43" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525025.&p=BOOKS&id=189922_ml366f43.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f43.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525025." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525025</span></h3></div><div id="ml366.f44" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525025.&p=BOOKS&id=189922_ml366f44.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f44.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525025." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525025</span></h3><div class="caption"><p>MW = 344.37</p></div></div><div id="ml366.f45" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525032.&p=BOOKS&id=189922_ml366f45.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f45.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525032." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525032</span></h3></div><div id="ml366.f46" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525032.&p=BOOKS&id=189922_ml366f46.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f46.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525032." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525032</span></h3><div class="caption"><p>MW = 430.45</p></div></div><div id="ml366.f47" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701487.&p=BOOKS&id=189922_ml366f47.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f47.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701487." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701487</span></h3></div><div id="ml366.f48" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701487.&p=BOOKS&id=189922_ml366f48.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f48.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701487." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701487</span></h3><div class="caption"><p>MW = 317.34</p></div></div><div id="ml366.f49" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2070701486.&p=BOOKS&id=189922_ml366f49.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f49.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 70701486." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 70701486</span></h3></div><div id="ml366.f50" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701486.&p=BOOKS&id=189922_ml366f50.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f50.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701486." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701486</span></h3><div class="caption"><p>MW = 373.31</p></div></div><div id="ml366.f51" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2070701501.&p=BOOKS&id=189922_ml366f51.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f51.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 70701501." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 70701501</span></h3></div><div id="ml366.f52" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701501.&p=BOOKS&id=189922_ml366f52.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f52.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701501." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701501</span></h3><div class="caption"><p>MW = 309.32</p></div></div><div id="ml366.f53" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701482.&p=BOOKS&id=189922_ml366f53.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f53.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701482." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701482</span></h3></div><div id="ml366.f54" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701482.&p=BOOKS&id=189922_ml366f54.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f54.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701482." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701482</span></h3><div class="caption"><p>MW = 389.38</p></div></div><div id="ml366.f55" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701504.&p=BOOKS&id=189922_ml366f55.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f55.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701504." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701504</span></h3></div><div id="ml366.f56" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701504.&p=BOOKS&id=189922_ml366f56.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f56.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701504." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701504</span></h3><div class="caption"><p>MW = 393.80</p></div></div><div id="ml366.f57" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701505.&p=BOOKS&id=189922_ml366f57.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f57.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701505." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701505</span></h3></div><div id="ml366.f58" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701505.&p=BOOKS&id=189922_ml366f58.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f58.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701505." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701505</span></h3><div class="caption"><p>MW = 274.28</p></div></div><div id="ml366.f59" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701491.&p=BOOKS&id=189922_ml366f59.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f59.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701491." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701491</span></h3></div><div id="ml366.f60" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701491.&p=BOOKS&id=189922_ml366f60.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f60.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701491." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701491</span></h3><div class="caption"><p>MW = 307.30</p></div></div><div id="ml366.f61" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-Acetone)%20of%20Analog%20CID%2028938024.&p=BOOKS&id=189922_ml366f61.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f61.jpg" alt="1H NMR Spectrum (300 MHz, d6-Acetone) of Analog CID 28938024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-Acetone) of Analog CID 28938024</span></h3></div><div id="ml366.f62" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2028938024.&p=BOOKS&id=189922_ml366f62.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f62.jpg" alt="UPLC-MS Chromatogram of Analog CID 28938024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 28938024</span></h3><div class="caption"><p>MW = 219.20</p></div></div><div id="ml366.f63" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%20676920.&p=BOOKS&id=189922_ml366f63.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f63.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 676920." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 676920</span></h3></div><div id="ml366.f64" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%20676920.&p=BOOKS&id=189922_ml366f64.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f64.jpg" alt="UPLC-MS Chromatogram of Analog CID 676920." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 676920</span></h3><div class="caption"><p>MW = 233.22</p></div></div><div id="ml366.f65" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701499.&p=BOOKS&id=189922_ml366f65.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f65.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701499." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701499</span></h3></div><div id="ml366.f66" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701499.&p=BOOKS&id=189922_ml366f66.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f66.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701499." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701499</span></h3><div class="caption"><p>MW = 244.25</p></div></div><div id="ml366.f67" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701502.&p=BOOKS&id=189922_ml366f67.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f67.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701502." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701502</span></h3></div><div id="ml366.f68" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701502.&p=BOOKS&id=189922_ml366f68.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f68.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701502." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701502</span></h3><div class="caption"><p>MW = 244.25</p></div></div><div id="ml366.f69" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701492.&p=BOOKS&id=189922_ml366f69.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f69.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701492." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701492</span></h3></div><div id="ml366.f70" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701492.&p=BOOKS&id=189922_ml366f70.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f70.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701492." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701492</span></h3><div class="caption"><p>MW = 297.35</p></div></div><div id="ml366.f71" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701484.&p=BOOKS&id=189922_ml366f71.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f71.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701484." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701484</span></h3></div><div id="ml366.f72" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701484.&p=BOOKS&id=189922_ml366f72.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f72.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701484." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701484</span></h3><div class="caption"><p>MW = 339.43</p></div></div><div id="ml366.f73" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701481.&p=BOOKS&id=189922_ml366f73.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f73.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701481." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701481</span></h3></div><div id="ml366.f74" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701481.&p=BOOKS&id=189922_ml366f74.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK189922/bin/ml366f74.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701481." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701481</span></h3><div class="caption"><p>MW = 286.33</p></div></div></div><div id="ml366.app8"><h2 id="_ml366_app8_">Appendix H. Compound Profiling Results</h2><div id="ml366.s39"><h3>Human kinase panel results</h3><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was profiled against a panel of 60 human kinases by Merck Millipore's KinaseProfiler™ service at a single concentration of 10 µM. Protein kinases are tested in a radiometric assay format and the raw data are measured by scintillation counting (in cpm).</p></div><div id="ml366.s40"><h3>Eurofins Radioligand binding assays</h3><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was screened against 67 targents with the LeadProfileScreen panel from Eurofins. Biochemical assay results are presented as the percent inhibition of specific binding or activity throughout the report. A significant response is considered anything greater than 50%. None of the assay results showed significant binding by <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>. Methods employed in this study have been adapted from the scientific literature to maximize reliability and reproducibility. Reference standards were run as an integral part of each assay to ensure the validity of the results obtained. Full assay conditions and references are available on the Eurofins website (<a href="http://www.eurofinspanlabs.com" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.eurofinspanlabs.com</a>).</p></div></div><div id="ml366.app9"><h2 id="_ml366_app9_">Appendix I. Alignment of LuxO Homologs in other pathogenic <i>Vibrio</i> species</h2><pre>
|
|
<i>V. cholerae</i> |mvedtasvaa --------------AVKEKSPDVPIVFMTAHGSIDTAVEAMRHGAQDFLI 36
|
|
<i>V. harveyi</i> |mqhtqslqka LRLPDMTGMDVLHAVKQKSPDVPIVFMTAHGSIDTAVEAMRHGAQDFLT 50
|
|
<i>V. mimicus</i> |mqlndihhka LRLPDMTGMDVLHAVKQRSPDVPVIFMTAHGSIDTAVEAMRHGAQDFLI 50
|
|
<i>V. vulnificus</i>|mqqitegqks LRLPDMTGMDVLHAVKKSHPDVPIIFMTAHGSIDTAVEAMRHGSQDFLI 50
|
|
<i>V. fluvialus</i> |mvedtasvaa -------------AVKASHPDVPIIFMTAHGSIDTAVEAMRHGSQDFLI 36
|
|
*** ****::******************:****
|
|
|
|
<i>V. cholerae</i> KPCEADRLRVTVNNAIRKASKLKNDVDNK-NQNYQGFIGSSQT<b>MQAVYRT</b> 85
|
|
<i>V. harveyi</i> KPCEADRLRVTVNNAIRKASKLKNDVDNK-NQNYQGFIGSSQT<b>MQAVYRT</b> 99
|
|
<i>V. mimicus</i> KPCEADRLRVTVNNAIRKASKLKNEADNPGNQNYQGFIGSSQT<b>MLAVYRT</b> 100
|
|
<i>V. vulnificus</i> KPCEADRLRVTVNNAIRKATKLKNEADNPGNQNYQGFIGSSQT<b>MQQVYRT</b> 100
|
|
<i>V. fluvialus</i> KPCEADRLRVTVNNAIRKASKLKNDADSAGSQNYQGFIGSSQK<b>MQQVYRT</b> 86
|
|
*******************:****:.*. .***********.* ****
|
|
|
|
<i>V. cholerae</i> <b>IDSAASSKASIFITGESGTGKEVCAEAIHAASKRGDKPFIAINCAAIPKD</b> 135
|
|
<i>V. harveyi</i> <b>IDSAASSKASIFITGESGTGKEVCAEAIHAASKRGDKPFIAINCAAIPKD</b> 149
|
|
<i>V. mimicus</i> <b>IDSAASSKASIFITGESGTGKEVCAEAIHAASRRGDKPFIAINCAAIPKD</b> 150
|
|
<i>V. vulnificus</i> <b>IDSAASSKASIFITGESGTGKEVCAEAIHAASKRGDKPFIAINCAAIPKD</b> 150
|
|
<i>V. fluvialus</i> <b>IDSAASSKASIFITGESGTGKEVCAEAIHAARRRGDKPFIAINCAAIPKD</b> 136
|
|
******************************* :*****************
|
|
|
|
<i>V. cholerae</i> <b>LIESELFGHVKGAFTGAATERQGAAEAADGGTLFLDELCEMDLDLQTKLL</b> 185
|
|
<i>V. harveyi</i> <b>LIESELFGHVKGAFTGAATERQGAAEAADGGTLFLDELCEMDLDLQTKLL</b> 199
|
|
<i>V. mimicus</i> <b>LIESELFGHVKGAFTGAATDRQGAAELADGGTLFLDELCEMDLDLQTKLL</b> 200
|
|
<i>V. vulnificus</i> <b>LIESELFGHVKGAFTGAANDRQGAAELADGGTLFLDELCEMDLDLQTKLL</b> 200
|
|
<i>V. fluvialus</i> <b>LIESELFGHVKGAFTGAATDRQGAAELADGGTLFLDELCEMDLDLQTKLL</b> 186
|
|
******************.:****** ***********************
|
|
|
|
<i>V. cholerae</i> <b>RFIQTGTFQKVGSSKMKSVDVRFVCATNRDPWKEVQEGRFREDLYYRLYV</b> 235
|
|
<i>V. harveyi</i> <b>RFIQTGTFQKVGSSKMKSVDVRFVCATNRDPWKEVQEGRFREDLYYRLYV</b> 249
|
|
<i>V. mimicus</i> <b>RFIQTGTFQKVGSSKMKSVDVRFVCATNRDPWKEVQEGRFREDLYYRLYV</b> 250
|
|
<i>V. vulnificus</i> <b>RFIQTGTFQKVGSSKMKSVDVRFVCATNRDPWKEVQEGRFREDLYYRLYV</b> 250
|
|
<i>V. fluvialus</i> <b>RFIQTGTFQKVGSSKMKSVDVRFVCATNRDPWKEVQEGRFREDLYYRLYV</b> 236
|
|
**************************************************
|
|
|
|
<i>V. cholerae</i> <b>IPLHLPP</b>LRARGDDVIEIAYSLLGFMSKEEGKDFVRLSAEVVERFRQYEW 285
|
|
<i>V. harveyi</i> <b>IPLHLPP</b>LRARGDDVIEIAYSLLGFMSKEEGKDFIRLSAEVVERFRHYEW 299
|
|
<i>V. mimicus</i> <b>IPLHLPP</b>LRERGDDVIEIAYSLLGYMSKEEGKGFVRLAPEVVERFKQYEW 300
|
|
<i>V. vulnificus</i> <b>IPLHLPP</b>LRERGEDVIEIAYSLLGYMSHEEGKSFIRFAQDVIERFNSYEW 300
|
|
<i>V. fluvialus</i> <b>IPLHLPP</b>LRERGEDVIEIAYSLLGYMSHEEGKNFVRFSQPVIDRFNEYEW 286
|
|
<b>*******</b>** **:***********:**:****.*:*:: *::**. ***
|
|
|
|
<i>V. cholerae</i> PGNVRQLQNVLRNVVVLNEGREITLDMLPPPLNQMSAPINRALPLAHEN- 334
|
|
<i>V. harveyi</i> PGNVRQLQNVLRNVVVLNEGREITLDMLPPPLNQMPEPVNRALPLANENK 349
|
|
<i>V. mimicus</i> PGNVRQLQNVLRNVVVLNEGREITLNMLPPPLNQPSESIISVPKASVAP- 349
|
|
<i>V. vulnificus</i> PGNVRQLQNVLRNIVVLNNGKEITLDMLPPPLNQPVVRQSISKFIEPEI- 349
|
|
<i>V. fluvialus</i> PGNVRQLQNVLRNVVVLNNGKEITMEMLPPPLNQPFERKESVQPDLSEL- 335
|
|
*************:****:*:***::********
|
|
|
|
<i>V. cholerae</i> KVSVHEIFPLWMTEKQAIEQAIEACDGNIPRAATYLDVSPSTIYRKLQTW 384
|
|
<i>V. harveyi</i> VVSVHEIFPLWMTEKQAIEQAIEACDGNIPRAATYLDVSPSTIYRKLQAW 399
|
|
<i>V. mimicus</i> -VSVHEIFPLWMTEKQAIEKAIEACDGNIPRAAGYLDVSPSTIYRKLQTW 398
|
|
<i>V. vulnificus</i> -MTVSDIMPLWMTEKMAIEQAIQACDGNIPRAAGYLDVSPSTIYRKLQAW 398
|
|
<i>V. fluvialus</i> -ISVRDICPLWLTEKLAIEQAIKACDGNIPRAAGYLDVSPSTIYRKLQAW 384
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::* :* ***:*** ***:**:********** **************:*
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<i>V. cholerae</i> NEKVKEKEKER 395 --
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<i>V. harveyi</i> NEKVKEKEKER 410 84.05%
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<i>V. mimicus</i> NEKVQEKEK-- 407 97.72%
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<i>V. vulnificus</i> NSKD-EKQNV- 407 84.48%
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<i>V. fluvialus</i> NEKE-EKQKA- 393 91.14%
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*.* **::
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_____
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Percent ID
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</pre></div><div id="ml366.app10"><h2 id="_ml366_app10_">Appendix J. Compounds Provided to Evotec</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml366t18"><a href="/books/NBK189922/table/ml366.t18/?report=objectonly" target="object" title="Table A3" class="img_link icnblk_img figpopup" rid-figpopup="figml366t18" rid-ob="figobml366t18"><img class="small-thumb" src="/books/NBK189922/table/ml366.t18/?report=thumb" src-large="/books/NBK189922/table/ml366.t18/?report=previmg" alt="Table A3. Probe and Analog Information." /></a><div class="icnblk_cntnt"><h4 id="ml366.t18"><a href="/books/NBK189922/table/ml366.t18/?report=objectonly" target="object" rid-ob="figobml366t18">Table A3</a></h4><p class="float-caption no_bottom_margin">Probe and Analog Information. </p></div></div></div><div style="display:none"><div style="display:none" id="figml366f9"><img alt="Image ml366f9" src-large="/books/NBK189922/bin/ml366f9.jpg" /></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK189922_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Patrick Faloon</span>,<sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup><sup>1</sup> <span itemprop="author">Ivan Jewett</span>,<sup>1</sup> <span itemprop="author">Willmen Youngsaye</span>,<sup>1</sup> <span itemprop="author">Melissa Bennion</span>,<sup>1</sup> <span itemprop="author">Wai-Leung Ng</span>,<sup>2,3</sup> <span itemprop="author">Amanda Hurley</span>,<sup>2</sup> <span itemprop="author">Timothy A. Lewis</span>,<sup>1</sup> <span itemprop="author">Rahul V. Edwankar</span>,<sup>1</sup> <span itemprop="author">Hanh Le</span>,<sup>1</sup> <span itemprop="author">Carrie M. Mosher</span>,<sup>1</sup> <span itemprop="author">Stephen Johnston</span>,<sup>1</sup> <span itemprop="author">Sivaraman Dandapani</span>,<sup>1</sup> <span itemprop="author">Benito Munoz</span>,<sup>1</sup> <span itemprop="author">Michelle Palmer</span>,<sup>1</sup> <span itemprop="author">Bonnie L. Bassler</span>,<sup>2</sup> and <span itemprop="author">Stuart L. Schreiber</span><sup>1,4,5</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup>
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The Broad Institute Probe Development Center, Cambridge, MA</div><div class="affiliation"><sup>2</sup>
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Princeton University, Princeton, NJ</div><div class="affiliation"><sup>3</sup>
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Tufts University, Sackler School of Graduate Biomedical Sciences, Boston, MA</div><div class="affiliation"><sup>4</sup>
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Chemical Biology Program, Broad Institute</div><div class="affiliation"><sup>5</sup>
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Department of Chemistry & Chemical Biology, Harvard University</div><div class="affiliation"><sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup>Corresponding author email:
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<a href="mailto:dev@null" data-email="gro.etutitsnidaorb@rebierhcs" class="oemail">gro.etutitsnidaorb@rebierhcs</a></div><h3>Publication History</h3><p class="small">Received: <span itemprop="datePublished">April 12, 2013</span>; Last Update: <span itemprop="dateModified">September 18, 2014</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p>National Center for Biotechnology Information (US), Bethesda (MD)</p><h3>NLM Citation</h3><p>Faloon P, Jewett I, Youngsaye W, et al. Discovery of ML366, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator. 2013 Apr 12 [Updated 2014 Sep 18]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/mlprobe/ml367/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/mlprobe/ml365/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="fig" id="figobml366f1"><div id="ml366.f1" class="figure"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20ml366f1&p=BOOKS&id=189922_ml366f1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f1.jpg" alt="Image ml366f1" class="tileshop" title="Click on image to zoom" /></a></div></div></article><article data-type="table-wrap" id="figobml366t1"><div id="ml366.t1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ml366.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubChem CID</th><th id="hd_h_ml366.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Targets</th><th id="hd_h_ml366.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> (µM)<br />[SID, AID]</th><th id="hd_h_ml366.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti-Target</th><th id="hd_h_ml366.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> (µM)<br />[SID, AID]</th><th id="hd_h_ml366.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Fold Selective<sup>*</sup></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t1_1_1_1_1" rowspan="4" colspan="1" style="text-align:center;vertical-align:middle;">CID 4443990</td><td headers="hd_h_ml366.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578</td><td headers="hd_h_ml366.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1<br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>,<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652239" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 652239</a>]</td><td headers="hd_h_ml366.t1_1_1_1_4" rowspan="4" colspan="1" style="text-align:center;vertical-align:middle;">HeLa cytotoxicity</td><td headers="hd_h_ml366.t1_1_1_1_5" rowspan="4" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>,<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686928</a>]</td><td headers="hd_h_ml366.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>14</td></tr><tr><td headers="hd_h_ml366.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1651</td><td headers="hd_h_ml366.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7<br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652289" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 652289</a>]</td><td headers="hd_h_ml366.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>13</td></tr><tr><td headers="hd_h_ml366.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> DH231</td><td headers="hd_h_ml366.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.7<br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686391" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686391</a>]</td><td headers="hd_h_ml366.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>20</td></tr><tr><td headers="hd_h_ml366.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> WN1103</td><td headers="hd_h_ml366.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.3<br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686390" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686390</a>]</td><td headers="hd_h_ml366.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>15</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>*</dt><dd><div id="ml366.tfn1"><p class="no_margin">Selectivity = Cytotoxicity IC<sub>50</sub>/Target EC<sub>50</sub></p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml366f2"><div id="ml366.f2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK189922/bin/ml366f2.jpg" alt="Figure 1. The Endogenous Ligand of the Vibrio cholerae Sensor Histidine Kinase CqsS, CAI-1." /></div><h3><span class="label">Figure 1</span><span class="title">The Endogenous Ligand of the <i>Vibrio cholerae</i> Sensor Histidine Kinase CqsS, CAI-1</span></h3><div class="caption"><p>Cholera autoinducer-1 (CAI-1)</p></div></div></article><article data-type="fig" id="figobml366f3"><div id="ml366.f3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20The%20V.%20cholerae%20CqsS%2FCAI-1%20Quorum%20Sensing%20Phosphorelay%20system.&p=BOOKS&id=189922_ml366f3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f3.jpg" alt="Figure 2. The V. cholerae CqsS/CAI-1 Quorum Sensing Phosphorelay system." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">The <i>V. cholerae</i> CqsS/CAI-1 Quorum Sensing Phosphorelay system</span></h3><div class="caption"><p>At low cell density, there are insufficient amounts of CAI-1 to adequately bind CqsS. This leads to the production of AphA and the adoption of individual cell behaviors. At high cell density, enough CAI-1 is present to bind CqsS effectively. This promotes the expression of HapR, and cells will now exhibit quorum behavior (Figure is adapted from reference <a class="bibr" href="#ml366.r10" rid="ml366.r10">10</a>).</p></div></div></article><article data-type="fig" id="figobml366f4"><div id="ml366.f4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20Aza-uracil-derived%20antagonists%20of%20LuxO%20ATPase%20activity.&p=BOOKS&id=189922_ml366f4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f4.jpg" alt="Figure 3. Aza-uracil-derived antagonists of LuxO ATPase activity." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">Aza-uracil-derived antagonists of LuxO ATPase activity</span></h3><div class="caption"><p>Aza-U (<b>4</b>) and its analogs have been shown to inhibit the ATPase activity of LuxO. Quorum-sensing modulation was measured in <i>V. cholera</i> strains BH1578 and BH1651 (see <a href="#ml366.s5">Section 2</a>) and their respective EC<sub>50</sub> values are estimated from the published dose-response curves [<a class="bibr" href="#ml366.r2" rid="ml366.r2">2</a>].</p></div></div></article><article data-type="table-wrap" id="figobml366t2"><div id="ml366.t2" class="table"><h3><span class="label">Table 1</span><span class="title">Strains of <i>V. cholera</i> used in assays</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Strain</th><th id="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Genotype</th><th id="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reporter</th><th id="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Suggested Mechanism for Inducers</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BH1578</td><td headers="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Δ<i>luxS</i> Δ<i>cqsA</i></td><td headers="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. harveyi</i> luciferase operon</td><td headers="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Multiple Mechanisms possible</td></tr><tr><td headers="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BH1651</td><td headers="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>luxO<sup>D47E</sup></i></td><td headers="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. harveyi</i> luciferase operon</td><td headers="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxO inhibitor or downstream</td></tr><tr><td headers="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">DH231</td><td headers="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Δ<i>luxS</i> Δ<i>cqsS</i></td><td headers="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. harveyi</i> luciferase operon</td><td headers="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxPQ agonist or LuxO inhibition</td></tr><tr><td headers="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">WN1103</td><td headers="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Δ<i>luxQ</i> Δ<i>cqsA</i></td><td headers="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. harveyi</i> luciferase operon</td><td headers="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CqsS agonist or LuxO inhibition</td></tr><tr><td headers="hd_h_ml366.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SLS353</td><td headers="hd_h_ml366.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>luxO<sup>D47E</sup></i></td><td headers="hd_h_ml366.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">qrr4:GFP reporter</td><td headers="hd_h_ml366.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxO inhibitor or downstream</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml366t3"><div id="ml366.t3" class="table"><h3><span class="label">Table 2</span><span class="title">Solubility of ML366 and Analogs in PBS and LB Assay Media</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t3_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t3_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml366.t3_1_1_1_1" style="text-align:center;vertical-align:middle;">PubChem CID / ML</th><th id="hd_h_ml366.t3_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ml366.t3_1_1_1_2" style="text-align:center;vertical-align:middle;">Structure</th><th id="hd_h_ml366.t3_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Solubility (µM)</th></tr><tr><th headers="hd_h_ml366.t3_1_1_1_3" id="hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>PBS</i><br /><i>w/ 1% DMSO</i></th><th headers="hd_h_ml366.t3_1_1_1_3" id="hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>LB Media</i><br /><i>w/ 1% DMSO</i></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4443990<br /><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a></td><td headers="hd_h_ml366.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu1.jpg" alt="Image ml366fu1.jpg" /></div></td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.7</td></tr><tr><td headers="hd_h_ml366.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525030</td><td headers="hd_h_ml366.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu2.jpg" alt="Image ml366fu2.jpg" /></div></td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.8</td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.1</td></tr><tr><td headers="hd_h_ml366.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525038</td><td headers="hd_h_ml366.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu3.jpg" alt="Image ml366fu3.jpg" /></div></td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7</td></tr><tr><td headers="hd_h_ml366.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4160355</td><td headers="hd_h_ml366.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu4.jpg" alt="Image ml366fu4.jpg" /></div></td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.0</td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.8</td></tr><tr><td headers="hd_h_ml366.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5084468</td><td headers="hd_h_ml366.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu5.jpg" alt="Image ml366fu5.jpg" /></div></td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.1</td><td headers="hd_h_ml366.t3_1_1_1_3 hd_h_ml366.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.1</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml366f5"><div id="ml366.f5" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20Stability%20of%20Probe%20ML366%20in%20PBS%20Buffer%20(pH%207.4%2C%2023%B0C).&p=BOOKS&id=189922_ml366f5.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f5.jpg" alt="Figure 4. Stability of Probe ML366 in PBS Buffer (pH 7.4, 23°C)." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">Stability of Probe ML366 in PBS Buffer (pH 7.4, 23°C)</span></h3></div></article><article data-type="table-wrap" id="figobml366t4"><div id="ml366.t4" class="table"><h3><span class="label">Table 3</span><span class="title">Plasma Stability and Plasma Binding of ML366</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t4_lrgtbl__"><table class="no_top_margin"><tbody><tr><td colspan="2" rowspan="1" style="text-align:left;vertical-align:middle;">GSH stability<br />(% remaining after 6 hours)</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99%</td></tr><tr><td rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Plasma stability<br />(% remaining after 5 hours)</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Human</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98%</td></tr><tr><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Murine</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0%</td></tr><tr><td rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Plasma protein binding<br />(% bound)</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Human</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98%</td></tr><tr><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Murine</td><td rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><10%</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml366t5"><div id="ml366.t5" class="table"><h3><span class="label">Table 4</span><span class="title">Summary of Probe Properties Computed for ML366</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t5_lrgtbl__"><table class="no_top_margin"><tbody><tr><th id="hd_b_ml366.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Probe</th><td headers="hd_b_ml366.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a></td></tr><tr><th id="hd_b_ml366.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">IUPAC Chemical Name</th><td headers="hd_b_ml366.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>N</i>-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl)cyclohexanecarboxamide</td></tr><tr><th id="hd_b_ml366.t5_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PubChem CID</th><td headers="hd_b_ml366.t5_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4443990</td></tr><tr><th id="hd_b_ml366.t5_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Molecular Formula</th><td headers="hd_b_ml366.t5_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">C<sub>17</sub>H<sub>19</sub>N<sub>3</sub>O<sub>4</sub></td></tr><tr><th id="hd_b_ml366.t5_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Molecular Weight (g/mol)</th><td headers="hd_b_ml366.t5_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">329.35</td></tr><tr><th id="hd_b_ml366.t5_1_1_6_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exact Mass (amu)</th><td headers="hd_b_ml366.t5_1_1_6_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">329.137556</td></tr><tr><th id="hd_b_ml366.t5_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XlogP3-AA</th><td headers="hd_b_ml366.t5_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7</td></tr><tr><th id="hd_b_ml366.t5_1_1_8_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Topological Surface Area</th><td headers="hd_b_ml366.t5_1_1_8_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">86.5</td></tr><tr><th id="hd_b_ml366.t5_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">H-Bond Donors</th><td headers="hd_b_ml366.t5_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td></tr><tr><th id="hd_b_ml366.t5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">H-Bond Acceptors</th><td headers="hd_b_ml366.t5_1_1_10_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td></tr><tr><th id="hd_b_ml366.t5_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rotatable Bond Count</th><td headers="hd_b_ml366.t5_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml366f6"><div id="ml366.f6" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Scheme%201.%20Synthesis%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f6.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f6.jpg" alt="Scheme 1. Synthesis of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Scheme 1</span><span class="title">Synthesis of Probe ML366</span></h3></div></article><article data-type="fig" id="figobml366f7"><div id="ml366.f7" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%205.%20Representative%20Dose%20Response%20Curves%20for%20Samples%20of%20CID%204443990.&p=BOOKS&id=189922_ml366f7.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f7.jpg" alt="Figure 5. Representative Dose Response Curves for Samples of CID 4443990." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 5</span><span class="title">Representative Dose Response Curves for Samples of CID 4443990</span></h3><div class="caption"><p>CID 4443990 was tested across a range of concentrations up to 35 µM in the primary assay and the BH1651 assay. Concentration response curves were generated with Genedata Screener Condoseo and show normalized percent activity for the individual doses. Note that the Y-axis scale differs greatly between assays and Figure B is relative luminescence units. BH1578 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/602243" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 602243</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/substance/24783538" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 24783538</a>), AC<sub>50</sub> = 9.4 µM (<i>A</i>); BH1651 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624254" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 624254</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/substance/24783538" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 24783538</a>), AC<sub>50</sub> = 4 µM (<i>B</i>); BH1578 assay <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> vs. AzaU (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686929" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686929</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>), <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> AC<sub>50</sub> = 2.1 µM (Green) AzaU AC<sub>50</sub> = 15.6 µM (Blue) Vertical strip of data points at right side represents single concentration sample wells of AzaU used as positive controls (<i>C</i>); BH1651 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652239" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 652239</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a>), AC<sub>50</sub> = 2.7 µM (<i>D</i>). <a href="https://pubchem.ncbi.nlm.nih.gov/substance/24783538" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 24783538</a> is a DMSO solution of CID 4443990 provided by EvoTec for the primary HTS. <a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 137282758</a> is a re-synthesized sample of CID 4443990. ○ = replicate 1, △ = replicate 2.</p></div></div></article><article data-type="fig" id="figobml366f8"><div id="ml366.f8" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%206.%20Critical%20Path%20for%20Probe%20Development.&p=BOOKS&id=189922_ml366f8.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f8.jpg" alt="Figure 6. Critical Path for Probe Development." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 6</span><span class="title">Critical Path for Probe Development</span></h3></div></article><article data-type="fig" id="figobml366f9"><div id="ml366.f9" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20ML366%20Induces%20Quorum%20Sensing%20via%20LuxO%20ATPase%20Inhibition%20without%20Toxicity.&p=BOOKS&id=189922_ml366f9.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f9.jpg" alt="Figure 7. ML366 Induces Quorum Sensing via LuxO ATPase Inhibition without Toxicity." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">ML366 Induces Quorum Sensing via LuxO ATPase Inhibition without Toxicity</span></h3><div class="caption"><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> was tested across a range of concentrations up to 35 µM in the primary BH1578 assay, the SLS353 qrr4:GFP reporter assay, the <i>in vitro</i> LuxO ATPase assay and a HeLa cytotoxicity assay. Concentration response curves were generated with Genedata Screener Condoseo and show normalized percent activity for the individual doses. DH231 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686931" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686931</a>), IC<sub>50</sub> = 2.1 µM (<i>A</i>); SLS353 assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686942" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686942</a>) (<i>B</i>); <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a>
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<i>in vitro</i> LuxO ATPase assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686936" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686936</a>) (<i>C</i>); <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> HeLa CellTiter-Glo (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 686928</a>), IC<sub>50</sub> ≥ 35 µM (D). ○ = replicate 1, △ = replicate 2. RFU=relative fluorescence unit.</p></div></div></article><article data-type="table-wrap" id="figobml366t6"><div id="ml366.t6" class="table"><h3><span class="label">Table 5</span><span class="title">PubChem Assays Reporting Dose-Dependent Activity of ML366<sup>†</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t6_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No.</th><th id="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubChem AID</th><th id="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubChem Assay</th><th id="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reported outcome</th><th id="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reported AC<sub>50</sub></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2288" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2288</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for Modulators of miRNAs and/or Activators of miR-21</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inactive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.5 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2289" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2289</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for Modulators of miRNAs and/or Inhibitors of miR-21</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.5 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/485297" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">485297</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for Rab9 Promoter Activators</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Active</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.5 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588342" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">588342</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS profiling assay for firefly luciferase inhibitor/activator using purified enzyme and Km concentrations of substrates</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/485313" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">485313</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for NPC1 Promoter Activator</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Active</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.5 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540253" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">540253</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for Inhibitors of RanGTP induced Rango (Ran-regulated importin-beta cargo) - Importin beta complex dissociation</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inactive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.6 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504466" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">504466</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS screen for small molecules that induce genotoxicity in human embryonic kidney (HEK293T) cells expressing luciferase-tagged ELG1</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.8 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540256" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">540256</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS for Inhibitors of binding or entry into cells for Lassa Virus</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.3 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1458" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1458</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS Assay for Enhancers of SMN2 Splice Variant Expression</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10.0 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504467" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">504467</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">qHTS screen for small molecules that inhibit ELG1-dependent DNA repair in human embryonic kidney (HEK293T) cells expressing luciferase-tagged ELG1</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11.5 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2546" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2546</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">VP16 counterscreen qHTS for inhibitors of ROR gamma transcriptional activity</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12.6 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504832" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">504832</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 48 hour incubation</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inactive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13.1 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504834" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">504834</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 96 hour incubation</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inactive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13.1 µM</td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/434987" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">434987</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screen and Counter Screen to Identify Novel Compounds that Selectively Sensitize Mycobacterium Tuberculosis to Beta-lactam Antibiotics</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Active</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16.3µM<sup>#</sup></td></tr><tr><td headers="hd_h_ml366.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15</td><td headers="hd_h_ml366.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504444" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">504444</a></td><td headers="hd_h_ml366.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nrf2 qHTS screen for inhibitors</td><td headers="hd_h_ml366.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconclusive</td><td headers="hd_h_ml366.t6_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16.4 µM</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn2"><p class="no_margin">Assay results are current as of July 23, 2013</p></div></dd></dl><dl class="bkr_refwrap"><dt>#</dt><dd><div id="ml366.tfn3"><p class="no_margin">Value reported as IC<sub>90</sub></p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml366f10"><div id="ml366.f10" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%208.%20Aminothiadiazole-containing%20Inhibitors%20of%20the%20EP3%20Receptor.&p=BOOKS&id=189922_ml366f10.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f10.jpg" alt="Figure 8. Aminothiadiazole-containing Inhibitors of the EP3 Receptor." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 8</span><span class="title">Aminothiadiazole-containing Inhibitors of the EP<sub>3</sub> Receptor</span></h3></div></article><article data-type="table-wrap" id="figobml366t7"><div id="ml366.t7" class="table"><h3><span class="label">Table 6</span><span class="title">Examination of the Benzodioxane System</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t7_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t7_1_1_1_1" colspan="9" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu6.jpg" alt="Image ml366fu6.jpg" /></div></th></tr><tr><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" id="hd_h_ml366.t7_1_1_2_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">No.</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" id="hd_h_ml366.t7_1_1_2_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID<br />SID<br />Broad ID</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" id="hd_h_ml366.t7_1_1_2_3" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">P/S<sup>†</sup></th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" id="hd_h_ml366.t7_1_1_2_4" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">R</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" id="hd_h_ml366.t7_1_1_2_5" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">PBS Solubility (µM)</th><th headers="hd_h_ml366.t7_1_1_1_1" id="hd_h_ml366.t7_1_1_2_6" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" id="hd_h_ml366.t7_1_1_2_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">HeLa Toxicity<br />[IC<sub>50</sub>, µM]<br />(n = 2)</th></tr><tr><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6" id="hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">n</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6" id="hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> (µM)</th><th headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6" id="hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Max. Response<sup>‡</sup></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<br />(hit)</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4443990<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282758</a><br />BRD-K53995654-001-07-6</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu7.jpg" alt="Image ml366fu7.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">146%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5111732<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844174" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844174</a><br />BRD-K73040374-001-01-9</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu8.jpg" alt="Image ml366fu8.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.8</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">23%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5084468<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844165" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844165</a><br />BRD-K93752547-001-06-6</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu9.jpg" alt="Image ml366fu9.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.1</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3474144<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844182" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844182</a><br />BRD-K87634321-001-01-7</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu10.jpg" alt="Image ml366fu10.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">93</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4160355<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844170" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844170</a><br />BRD-K72622953-001-06-3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu11.jpg" alt="Image ml366fu11.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.0</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16854334<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844169" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844169</a><br />BRD-K83183415-001-01-6</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu12.jpg" alt="Image ml366fu12.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5170103<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844180" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844180</a><br />BRD-K31333480-001-01-0</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu13.jpg" alt="Image ml366fu13.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7158403<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844181" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844181</a><br />BRD-K21011860-001-01-4</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu14.jpg" alt="Image ml366fu14.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">92</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701498<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844183" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844183</a><br />BRD-K78774437-001-01-3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu15.jpg" alt="Image ml366fu15.jpg" /></div></td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">99</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_6 hd_h_ml366.t7_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t7_1_1_1_1 hd_h_ml366.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn4"><p class="no_margin">P = purchased; S = synthesized</p></div></dd></dl><dl class="bkr_refwrap"><dt>‡</dt><dd><div id="ml366.tfn5"><p class="no_margin">Percent maximal bioluminescence relative to Aza-U, which is set at 100%.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div id="ml366.tfn6"><p class="no_margin">n = number of independent experiments, performed in duplicate</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml366t8"><div id="ml366.t8" class="table"><h3><span class="label">Table 7</span><span class="title">Biological Activity of Various Amides and Amine Substituents</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t8_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t8_1_1_1_1" colspan="9" rowspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu16.jpg" alt="Image ml366fu16.jpg" /></div></th></tr><tr><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" id="hd_h_ml366.t8_1_1_2_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">No.</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" id="hd_h_ml366.t8_1_1_2_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID<br />SID<br />Broad ID</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" id="hd_h_ml366.t8_1_1_2_3" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">P/S<sup>†</sup></th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" id="hd_h_ml366.t8_1_1_2_4" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">R</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" id="hd_h_ml366.t8_1_1_2_5" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">PBS Solubility (µM)</th><th headers="hd_h_ml366.t8_1_1_1_1" id="hd_h_ml366.t8_1_1_2_6" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" id="hd_h_ml366.t8_1_1_2_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">HeLa Toxicity<br />[IC<sub>50</sub>, µM]<br />(n =)</th></tr><tr><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6" id="hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">n</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6" id="hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> (µM)</th><th headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6" id="hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Max. Response<sup>‡</sup></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<br />(hit)</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4443990<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282758</a><br />BRD-K53995654-001-07-6</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu17.jpg" alt="Image ml366fu17.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">146%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4420019<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282741" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282741</a><br />BRD-K53454226-001-01-6</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu18.jpg" alt="Image ml366fu18.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525024<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282757" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282757</a><br />BRD-K74968302-001-01-7</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu19.jpg" alt="Image ml366fu19.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525030<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282751" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282751</a><br />BRD-K76812495-001-01-2</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu20.jpg" alt="Image ml366fu20.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.8</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525038<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282753" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282753</a><br />BRD-K40011623-001-01-9</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu21.jpg" alt="Image ml366fu21.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">34.0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">60%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525031<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282756" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282756</a><br />BRD-K86555403-001-01-6</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu22.jpg" alt="Image ml366fu22.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">60</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525025<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282726" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282726</a><br />BRD-K28627761-001-01-0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu23.jpg" alt="Image ml366fu23.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>100</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525032<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282735" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282735</a><br />BRD-K90588892-001-01-9</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu24.jpg" alt="Image ml366fu24.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701487<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844171" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844171</a><br />BRD-K95071303-001-01-4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu25.jpg" alt="Image ml366fu25.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.9</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701486<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844166" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844166</a><br />BRD-K36208737-001-01-0</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu26.jpg" alt="Image ml366fu26.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">89</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701501<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844167" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844167</a><br />BRD-K73520786-001-01-2</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu27.jpg" alt="Image ml366fu27.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701482<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844172" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844172</a><br />BRD-K00837228-001-01-4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu28.jpg" alt="Image ml366fu28.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>100</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701504<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844173" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844173</a><br />BRD-K40332792-001-01-4</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu29.jpg" alt="Image ml366fu29.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">72</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701505<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844168" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844168</a><br />BRD-K50106655-001-01-5</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu30.jpg" alt="Image ml366fu30.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701491<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844178" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844178</a><br />BRD-K11631459-001-01-8</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu31.jpg" alt="Image ml366fu31.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">59</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">28938024<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282749" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282749</a><br />BRD-K05519962-001-01-3</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu32.jpg" alt="Image ml366fu32.jpg" /></div></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>100</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_6 hd_h_ml366.t8_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t8_1_1_1_1 hd_h_ml366.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn7"><p class="no_margin">P = purchased; S = synthesized</p></div></dd></dl><dl class="bkr_refwrap"><dt>‡</dt><dd><div id="ml366.tfn8"><p class="no_margin">Percent maximal bioluminescence relative to Aza-U, which is set at 100%.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div id="ml366.tfn9"><p class="no_margin">n = number of independent experiments, performed in duplicate</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml366t9"><div id="ml366.t9" class="table"><h3><span class="label">Table 8</span><span class="title">Different Combinations of Amides and Benzodioxane Replacements</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t9/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t9_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t9_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_1" style="text-align:center;vertical-align:middle;">No.</th><th id="hd_h_ml366.t9_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_2" style="text-align:center;vertical-align:middle;">CID<br />SID<br />Broad ID</th><th id="hd_h_ml366.t9_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_3" style="text-align:center;vertical-align:middle;">P/S<sup>†</sup></th><th id="hd_h_ml366.t9_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_4" style="text-align:center;vertical-align:middle;">R</th><th id="hd_h_ml366.t9_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_5" style="text-align:center;vertical-align:middle;">PBS Solubility (µM)</th><th id="hd_h_ml366.t9_1_1_1_6" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578</th><th id="hd_h_ml366.t9_1_1_1_7" rowspan="2" colspan="1" headers="hd_h_ml366.t9_1_1_1_7" style="text-align:center;vertical-align:middle;">HeLa Toxicity<br />[IC<sub>50</sub>, µM]<br />(n = 2)</th></tr><tr><th headers="hd_h_ml366.t9_1_1_1_6" id="hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">n</th><th headers="hd_h_ml366.t9_1_1_1_6" id="hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> (µM)</th><th headers="hd_h_ml366.t9_1_1_1_6" id="hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Max. Response<sup>‡</sup></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<br />(hit)</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">676920<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844177" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844177</a><br />BRD-K66634618-001-01-4</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu33.jpg" alt="Image ml366fu33.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">84</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701499<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844184" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844184</a><br />BRD-K59802036-001-01-0</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu34.jpg" alt="Image ml366fu34.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701502<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844186" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844186</a><br />BRD-K50418994-001-01-4</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu35.jpg" alt="Image ml366fu35.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">95</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701492<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844179" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844179</a><br />BRD-K32612454-001-01-8</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu36.jpg" alt="Image ml366fu36.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701484<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844175" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844175</a><br />BRD-K93026875-001-01-8</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu37.jpg" alt="Image ml366fu37.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1.0</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701481<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844176" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844176</a><br />BRD-K24703846-001-01-2</td><td headers="hd_h_ml366.t9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml366.t9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu38.jpg" alt="Image ml366fu38.jpg" /></div></td><td headers="hd_h_ml366.t9_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">86</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t9_1_1_1_6 hd_h_ml366.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><1%</td><td headers="hd_h_ml366.t9_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn10"><p class="no_margin">P = purchased; S = synthesized</p></div></dd></dl><dl class="bkr_refwrap"><dt>‡</dt><dd><div id="ml366.tfn11"><p class="no_margin">Percent maximal bioluminescence relative to Aza-U, which is set at 100%.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div id="ml366.tfn12"><p class="no_margin">n = number of independent experiments, performed in duplicate</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml366t10"><div id="ml366.t10" class="table"><h3><span class="label">Table 9</span><span class="title">Comparison of the performance of ML366 to Project Criteria</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t10/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t10_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No.</th><th id="hd_h_ml366.t10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Property</th><th id="hd_h_ml366.t10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CPDP Requirement</th><th id="hd_h_ml366.t10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Probe <a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a></th></tr></thead><tbody><tr><td headers="hd_h_ml366.t10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml366.t10_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Light production in <i>V. cholerae</i> BH1578</td><td headers="hd_h_ml366.t10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> ≤ 10 µM</td><td headers="hd_h_ml366.t10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1 µM</td></tr><tr><td headers="hd_h_ml366.t10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t10_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">HeLa cytotoxicity</td><td headers="hd_h_ml366.t10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> ≥ 30 µM</td><td headers="hd_h_ml366.t10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35 µM</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml366f11"><div id="ml366.f11" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%209.%20Summary%20of%20Analogs%20Prepared%20to%20Investigate%20the%20SAR%20profile%20of%20hit%20CID%204443990.&p=BOOKS&id=189922_ml366f11.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f11.jpg" alt="Figure 9. Summary of Analogs Prepared to Investigate the SAR profile of hit CID 4443990." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 9</span><span class="title">Summary of Analogs Prepared to Investigate the SAR profile of hit CID 4443990</span></h3><div class="caption"><p>Key SAR findings for each site of diversification are provided in italics.</p></div></div></article><article data-type="table-wrap" id="figobml366t11"><div id="ml366.t11" class="table"><h3><span class="label">Table 10</span><span class="title">Comparison of Project Probes to Natural Ligand and Prior Art</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t11/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t11_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No.</th><th id="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound</th><th id="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">EC<sub>50</sub> BH1578 (µM)</th><th id="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Max. Response<sup>†</sup></th><th id="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> HeLa (µM)</th><th id="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Proposed Mechanism</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu39.jpg" alt="Image ml366fu39.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.1</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">76%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CqsS agonist</td></tr><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu40.jpg" alt="Image ml366fu40.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12.3</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxO antagonist</td></tr><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu41.jpg" alt="Image ml366fu41.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">146%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxO antagonist</td></tr><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu42.jpg" alt="Image ml366fu42.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.4</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">139%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">LuxO antagonist</td></tr><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu43.jpg" alt="Image ml366fu43.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.5</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">66%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CqsSagonist</td></tr><tr><td headers="hd_h_ml366.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu44.jpg" alt="Image ml366fu44.jpg" /></div></td><td headers="hd_h_ml366.t11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.0</td><td headers="hd_h_ml366.t11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">156%</td><td headers="hd_h_ml366.t11_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml366.t11_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CqsSagonist</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn13"><p class="no_margin">Percent maximal bioluminescence relative to Aza-U, which is set at 100%.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml366t12"><div id="ml366.t12" class="table"><h3><span class="label">Table 11</span><span class="title">Probe Activation of Quorum Sensing in <i>Vibrio cholerae</i> Mutant Strains</span></h3><div class="caption"><p><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> and several analogs were evaluated in alternative <i>V. cholerae</i> mutants to establish possible modes of action. The reported EC<sub>50</sub> values are the average of at least two independent experiments, performed in duplicate. NT = not tested due to known interaction with CqsS.</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t12/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t12_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ml366.t12_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml366.t12_1_1_1_1" style="text-align:center;vertical-align:middle;">No.</th><th id="hd_h_ml366.t12_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ml366.t12_1_1_1_2" style="text-align:center;vertical-align:middle;">CID<br />SID<br />Broad ID</th><th id="hd_h_ml366.t12_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ml366.t12_1_1_1_3" style="text-align:center;vertical-align:middle;">Structure<br />ML / Name</th><th id="hd_h_ml366.t12_1_1_1_4" colspan="5" rowspan="1" style="text-align:center;vertical-align:middle;"><i>Vibrio cholerae</i> strain EC<sub>50</sub>, µM<br />(Maximal response %)<sup>†</sup></th></tr><tr><th headers="hd_h_ml366.t12_1_1_1_4" id="hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BH1578<br />(<i>ΔcqsA</i>, <i>ΔluxS</i>)</th><th headers="hd_h_ml366.t12_1_1_1_4" id="hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BH1651<br />(<i>luxO<sup>D47E</sup></i>)</th><th headers="hd_h_ml366.t12_1_1_1_4" id="hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">DH231<br />(<i>ΔcqsS ΔluxS</i>)</th><th headers="hd_h_ml366.t12_1_1_1_4" id="hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">WN1103<br />(<i>ΔluxQ ΔcqsA</i>)</th><th headers="hd_h_ml366.t12_1_1_1_4" id="hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SLS353<br />(<i>luxO<sup>D47E</sup>, qrr4:GFP</i>)</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53262910<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124404431" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124404431</a><br />BRD-A83720548-001-01-7</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu45.jpg" alt="Image ml366fu45.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.1<br />(76%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0<br />(99%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td></tr><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70701493<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844164" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844164</a><br />BRD-K02410423-001-01-1</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu46.jpg" alt="Image ml366fu46.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12.3<br />(100%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(100%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(100%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21<br />(100%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16<br />(100%)</td></tr><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4443990<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282758</a><br />BRD-K53995654-001-07-6</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu47.jpg" alt="Image ml366fu47.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1<br />(146%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.7<br />(98%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.7<br />(92%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.1<br />(90%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.2</td></tr><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">70680248<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160655705" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160655705</a><br />BRD-K33563922-001-01-6</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu48.jpg" alt="Image ml366fu48.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.4<br />(139%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.9<br />(88%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.8<br />(86%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0<br />(106%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0</td></tr><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">57525036<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282727" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282727</a><br />BRD-K30958453-001-01-8</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu49.jpg" alt="Image ml366fu49.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.0<br />(156%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.7<br />(101%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml366.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml366.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4727493<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/144220011" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">144220011</a><br />BRD-K81170493-001-02-8</td><td headers="hd_h_ml366.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK189922/bin/ml366fu50.jpg" alt="Image ml366fu50.jpg" /></div></td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.5<br />(66%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35<br />(<1%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.3<br />(97%)</td><td headers="hd_h_ml366.t12_1_1_1_4 hd_h_ml366.t12_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn14"><p class="no_margin">This value is scaled relative to 40 µM Aza-U, which is set at 100%.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml366f12"><div id="ml366.f12" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2010.%20Possible%20directions%20for%20future%20SAR%20investigation%20of%20ML366.&p=BOOKS&id=189922_ml366f12.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f12.jpg" alt="Figure 10. Possible directions for future SAR investigation of ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 10</span><span class="title">Possible directions for future SAR investigation of ML366</span></h3></div></article><article data-type="table-wrap" id="figobml366t13"><div id="ml366.t13" class="table"><h3><span class="label">Table A1</span><span class="title">Summary of Completed Assays and AIDs</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t13/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t13_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubChem AID</th><th id="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Type</th><th id="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target</th><th id="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Concentration Range (µM)</th><th id="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Samples Tested</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588521" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">588521</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Summary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588346" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">588346</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">20</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">350,317</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/602243" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">602243</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.024-50</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">623</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624270" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624270</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651854" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651854</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651809" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651809</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.135-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">101</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651816" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651816</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652239" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">652239</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686929" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686929</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><i>V. cholerae</i> BH1578 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624140" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624140</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">HeLa mammalian cytotoxicity</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">27</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651774" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651774</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">HeLa mammalian cytotoxicity</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.135-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">101</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651864" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651864</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">HeLa mammalian cytotoxicity</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686928</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">HeLa mammalian cytotoxicity</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624254" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624254</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1651 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.024-50</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">623</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624269" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624269</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1651 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651847" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651847</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1651 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652289" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">652289</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> BH1651 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624281" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624281</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> DH231 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651808" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651808</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> DH 231 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686931" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686931</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> DH231 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/624275" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">624275</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> WN1103 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.00006-35</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/651841" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">651841</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> WN1103 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686930" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686930</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>V. cholerae</i> WN1103 bioluminescence</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.0000001-80</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">97</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/652219" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">652219</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SLS353 qrr4:GFP reporter assay</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.24-500</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686942" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686942</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SLS353 qrr4:GFP reporter assay</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.02-50</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td></tr><tr><td headers="hd_h_ml366.t13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/686936" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">686936</a></td><td headers="hd_h_ml366.t13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary</td><td headers="hd_h_ml366.t13_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">LuxO <i>in vitro</i> ATPase assay</td><td headers="hd_h_ml366.t13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1-100</td><td headers="hd_h_ml366.t13_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml366f13"><div id="ml366.f13" class="figure"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20ml366f13&p=BOOKS&id=189922_ml366f13.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f13.jpg" alt="Image ml366f13" class="tileshop" title="Click on image to zoom" /></a></div></div></article><article data-type="fig" id="figobml366f14"><div id="ml366.f14" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(500%20MHz%2C%20d6-DMSO)%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f14.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f14.jpg" alt="1H NMR Spectrum (500 MHz, d6-DMSO) of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (500 MHz, d<sub>6</sub>-DMSO) of Probe ML366</span></h3></div></article><article data-type="fig" id="figobml366f15"><div id="ml366.f15" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=13C%20NMR%20Spectrum%20(125%20MHz%2C%20d6-DMSO)%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f15.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f15.jpg" alt="13C NMR Spectrum (125 MHz, d6-DMSO) of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>13</sup>C NMR Spectrum (125 MHz, d<sub>6</sub>-DMSO) of Probe ML366</span></h3></div></article><article data-type="fig" id="figobml366f16"><div id="ml366.f16" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Probe%20ML366.&p=BOOKS&id=189922_ml366f16.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f16.jpg" alt="UPLC-MS Chromatogram of Probe ML366." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Probe ML366</span></h3></div></article><article data-type="table-wrap" id="figobml366t14"><div id="ml366.t14" class="table"><h3><span class="label">Table A2</span><span class="title">Search Strings and Databases Employed in Prior Art Search</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t14/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t14_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Search String</th><th id="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Database</th><th id="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Hits Found<br />(9 May 2011)</th><th id="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Hits Found<br />(2 Apr 2013)</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera LuxO”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SciFinder</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">19<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“LuxO antagonist”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SciFinder</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“LuxO inhibit”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SciFinder</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera quorum inhibit”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SciFinder</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">30<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera AND LuxO”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reaxys</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N/A</td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera AND quorum”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reaxys</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N/A</td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubChem Bioassay</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">80<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">105<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“LuxO”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubMed</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">63<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">76<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera quorum inhibit”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">PubMed</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera AND quorum”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">USPTO PatFT</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">27<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">40<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera AND quorum”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">USPTO AppFT</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">96<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">125<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“cholera AND quorum”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">WIPO</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">68<sup>*</sup></td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">95<sup>*</sup></td></tr><tr><td headers="hd_h_ml366.t14_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">“LuxO”</td><td headers="hd_h_ml366.t14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Thomson Reuters Integrity</td><td headers="hd_h_ml366.t14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N/A</td><td headers="hd_h_ml366.t14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3<sup>*</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>*</dt><dd><div id="ml366.tfn15"><p class="no_margin">Abstracts were obtained and analyzed for relevance for all hits generated from this search</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml366f17"><div id="ml366.f17" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%205111732.&p=BOOKS&id=189922_ml366f17.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f17.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 5111732." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 5111732</span></h3></div></article><article data-type="fig" id="figobml366f18"><div id="ml366.f18" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205111732.&p=BOOKS&id=189922_ml366f18.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f18.jpg" alt="UPLC-MS Chromatogram of Analog CID 5111732." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5111732</span></h3><div class="caption"><p>MW = 301.34</p></div></div></article><article data-type="fig" id="figobml366f19"><div id="ml366.f19" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%205084468.&p=BOOKS&id=189922_ml366f19.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f19.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 5084468." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 5084468</span></h3></div></article><article data-type="fig" id="figobml366f20"><div id="ml366.f20" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205084468.&p=BOOKS&id=189922_ml366f20.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f20.jpg" alt="UPLC-MS Chromatogram of Analog CID 5084468." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5084468</span></h3><div class="caption"><p>MW = 301.34</p></div></div></article><article data-type="fig" id="figobml366f21"><div id="ml366.f21" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%203474144.&p=BOOKS&id=189922_ml366f21.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f21.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 3474144." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 3474144</span></h3></div></article><article data-type="fig" id="figobml366f22"><div id="ml366.f22" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%203474144.&p=BOOKS&id=189922_ml366f22.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f22.jpg" alt="UPLC-MS Chromatogram of Analog CID 3474144." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 3474144</span></h3><div class="caption"><p>MW = 301.34</p></div></div></article><article data-type="fig" id="figobml366f23"><div id="ml366.f23" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%204160355.&p=BOOKS&id=189922_ml366f23.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f23.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 4160355." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 4160355</span></h3></div></article><article data-type="fig" id="figobml366f24"><div id="ml366.f24" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%204160355.&p=BOOKS&id=189922_ml366f24.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f24.jpg" alt="UPLC-MS Chromatogram of Analog CID 4160355." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 4160355</span></h3><div class="caption"><p>MW = 305.76</p></div></div></article><article data-type="fig" id="figobml366f25"><div id="ml366.f25" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2016854334.&p=BOOKS&id=189922_ml366f25.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f25.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 16854334." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 16854334</span></h3></div></article><article data-type="fig" id="figobml366f26"><div id="ml366.f26" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2016854334.&p=BOOKS&id=189922_ml366f26.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f26.jpg" alt="UPLC-MS Chromatogram of Analog CID 16854334." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 16854334</span></h3><div class="caption"><p>MW = 305.76</p></div></div></article><article data-type="fig" id="figobml366f27"><div id="ml366.f27" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%205170103.&p=BOOKS&id=189922_ml366f27.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f27.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 5170103." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 5170103</span></h3></div></article><article data-type="fig" id="figobml366f28"><div id="ml366.f28" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%205170103.&p=BOOKS&id=189922_ml366f28.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f28.jpg" alt="UPLC-MS Chromatogram of Analog CID 5170103." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 5170103</span></h3><div class="caption"><p>MW = 305.76</p></div></div></article><article data-type="fig" id="figobml366f29"><div id="ml366.f29" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%207158403.&p=BOOKS&id=189922_ml366f29.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f29.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 7158403." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 7158403</span></h3></div></article><article data-type="fig" id="figobml366f30"><div id="ml366.f30" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%207158403.&p=BOOKS&id=189922_ml366f30.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f30.jpg" alt="UPLC-MS Chromatogram of Analog CID 7158403." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 7158403</span></h3><div class="caption"><p>MW = 272.30</p></div></div></article><article data-type="fig" id="figobml366f31"><div id="ml366.f31" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701498.&p=BOOKS&id=189922_ml366f31.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f31.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701498." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701498</span></h3></div></article><article data-type="fig" id="figobml366f32"><div id="ml366.f32" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701498.&p=BOOKS&id=189922_ml366f32.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f32.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701498." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701498</span></h3><div class="caption"><p>MW = 263.34</p></div></div></article><article data-type="fig" id="figobml366f33"><div id="ml366.f33" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%204420019.&p=BOOKS&id=189922_ml366f33.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f33.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 4420019." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 4420019</span></h3></div></article><article data-type="fig" id="figobml366f34"><div id="ml366.f34" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%204420019.&p=BOOKS&id=189922_ml366f34.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f34.jpg" alt="UPLC-MS Chromatogram of Analog CID 4420019." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 4420019</span></h3><div class="caption"><p>MW = 287.27</p></div></div></article><article data-type="fig" id="figobml366f35"><div id="ml366.f35" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525024.&p=BOOKS&id=189922_ml366f35.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f35.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525024</span></h3></div></article><article data-type="fig" id="figobml366f36"><div id="ml366.f36" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525024.&p=BOOKS&id=189922_ml366f36.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f36.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525024</span></h3><div class="caption"><p>MW = 301.30</p></div></div></article><article data-type="fig" id="figobml366f37"><div id="ml366.f37" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525030.&p=BOOKS&id=189922_ml366f37.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f37.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525030." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525030</span></h3></div></article><article data-type="fig" id="figobml366f38"><div id="ml366.f38" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525030.&p=BOOKS&id=189922_ml366f38.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f38.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525030." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525030</span></h3><div class="caption"><p>MW = 315.32</p></div></div></article><article data-type="fig" id="figobml366f39"><div id="ml366.f39" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525038.&p=BOOKS&id=189922_ml366f39.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f39.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525038." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525038</span></h3></div></article><article data-type="fig" id="figobml366f40"><div id="ml366.f40" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525038.&p=BOOKS&id=189922_ml366f40.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f40.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525038." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525038</span></h3><div class="caption"><p>MW = 343.38</p></div></div></article><article data-type="fig" id="figobml366f41"><div id="ml366.f41" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525031.&p=BOOKS&id=189922_ml366f41.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f41.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525031." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525031</span></h3></div></article><article data-type="fig" id="figobml366f42"><div id="ml366.f42" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=LCMS%20Chromatogram%20of%20Analog%20CID%2057525031.&p=BOOKS&id=189922_ml366f42.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f42.jpg" alt="LCMS Chromatogram of Analog CID 57525031." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">LCMS Chromatogram of Analog CID 57525031</span></h3><div class="caption"><p>MW = 331.32</p></div></div></article><article data-type="fig" id="figobml366f43"><div id="ml366.f43" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525025.&p=BOOKS&id=189922_ml366f43.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f43.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525025." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525025</span></h3></div></article><article data-type="fig" id="figobml366f44"><div id="ml366.f44" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525025.&p=BOOKS&id=189922_ml366f44.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f44.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525025." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525025</span></h3><div class="caption"><p>MW = 344.37</p></div></div></article><article data-type="fig" id="figobml366f45"><div id="ml366.f45" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2057525032.&p=BOOKS&id=189922_ml366f45.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f45.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 57525032." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 57525032</span></h3></div></article><article data-type="fig" id="figobml366f46"><div id="ml366.f46" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2057525032.&p=BOOKS&id=189922_ml366f46.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f46.jpg" alt="UPLC-MS Chromatogram of Analog CID 57525032." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 57525032</span></h3><div class="caption"><p>MW = 430.45</p></div></div></article><article data-type="fig" id="figobml366f47"><div id="ml366.f47" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701487.&p=BOOKS&id=189922_ml366f47.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f47.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701487." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701487</span></h3></div></article><article data-type="fig" id="figobml366f48"><div id="ml366.f48" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701487.&p=BOOKS&id=189922_ml366f48.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f48.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701487." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701487</span></h3><div class="caption"><p>MW = 317.34</p></div></div></article><article data-type="fig" id="figobml366f49"><div id="ml366.f49" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2070701486.&p=BOOKS&id=189922_ml366f49.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f49.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 70701486." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 70701486</span></h3></div></article><article data-type="fig" id="figobml366f50"><div id="ml366.f50" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701486.&p=BOOKS&id=189922_ml366f50.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f50.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701486." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701486</span></h3><div class="caption"><p>MW = 373.31</p></div></div></article><article data-type="fig" id="figobml366f51"><div id="ml366.f51" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%2070701501.&p=BOOKS&id=189922_ml366f51.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f51.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 70701501." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 70701501</span></h3></div></article><article data-type="fig" id="figobml366f52"><div id="ml366.f52" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701501.&p=BOOKS&id=189922_ml366f52.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f52.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701501." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701501</span></h3><div class="caption"><p>MW = 309.32</p></div></div></article><article data-type="fig" id="figobml366f53"><div id="ml366.f53" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701482.&p=BOOKS&id=189922_ml366f53.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f53.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701482." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701482</span></h3></div></article><article data-type="fig" id="figobml366f54"><div id="ml366.f54" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701482.&p=BOOKS&id=189922_ml366f54.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f54.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701482." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701482</span></h3><div class="caption"><p>MW = 389.38</p></div></div></article><article data-type="fig" id="figobml366f55"><div id="ml366.f55" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701504.&p=BOOKS&id=189922_ml366f55.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f55.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701504." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701504</span></h3></div></article><article data-type="fig" id="figobml366f56"><div id="ml366.f56" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701504.&p=BOOKS&id=189922_ml366f56.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f56.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701504." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701504</span></h3><div class="caption"><p>MW = 393.80</p></div></div></article><article data-type="fig" id="figobml366f57"><div id="ml366.f57" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701505.&p=BOOKS&id=189922_ml366f57.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f57.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701505." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701505</span></h3></div></article><article data-type="fig" id="figobml366f58"><div id="ml366.f58" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701505.&p=BOOKS&id=189922_ml366f58.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f58.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701505." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701505</span></h3><div class="caption"><p>MW = 274.28</p></div></div></article><article data-type="fig" id="figobml366f59"><div id="ml366.f59" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701491.&p=BOOKS&id=189922_ml366f59.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f59.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701491." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701491</span></h3></div></article><article data-type="fig" id="figobml366f60"><div id="ml366.f60" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701491.&p=BOOKS&id=189922_ml366f60.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f60.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701491." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701491</span></h3><div class="caption"><p>MW = 307.30</p></div></div></article><article data-type="fig" id="figobml366f61"><div id="ml366.f61" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-Acetone)%20of%20Analog%20CID%2028938024.&p=BOOKS&id=189922_ml366f61.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f61.jpg" alt="1H NMR Spectrum (300 MHz, d6-Acetone) of Analog CID 28938024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-Acetone) of Analog CID 28938024</span></h3></div></article><article data-type="fig" id="figobml366f62"><div id="ml366.f62" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2028938024.&p=BOOKS&id=189922_ml366f62.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f62.jpg" alt="UPLC-MS Chromatogram of Analog CID 28938024." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 28938024</span></h3><div class="caption"><p>MW = 219.20</p></div></div></article><article data-type="fig" id="figobml366f63"><div id="ml366.f63" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20d6-DMSO)%20of%20Analog%20CID%20676920.&p=BOOKS&id=189922_ml366f63.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f63.jpg" alt="1H NMR Spectrum (300 MHz, d6-DMSO) of Analog CID 676920." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, d<sub>6</sub>-DMSO) of Analog CID 676920</span></h3></div></article><article data-type="fig" id="figobml366f64"><div id="ml366.f64" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%20676920.&p=BOOKS&id=189922_ml366f64.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f64.jpg" alt="UPLC-MS Chromatogram of Analog CID 676920." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 676920</span></h3><div class="caption"><p>MW = 233.22</p></div></div></article><article data-type="fig" id="figobml366f65"><div id="ml366.f65" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701499.&p=BOOKS&id=189922_ml366f65.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f65.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701499." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701499</span></h3></div></article><article data-type="fig" id="figobml366f66"><div id="ml366.f66" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701499.&p=BOOKS&id=189922_ml366f66.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f66.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701499." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701499</span></h3><div class="caption"><p>MW = 244.25</p></div></div></article><article data-type="fig" id="figobml366f67"><div id="ml366.f67" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701502.&p=BOOKS&id=189922_ml366f67.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f67.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701502." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701502</span></h3></div></article><article data-type="fig" id="figobml366f68"><div id="ml366.f68" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701502.&p=BOOKS&id=189922_ml366f68.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f68.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701502." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701502</span></h3><div class="caption"><p>MW = 244.25</p></div></div></article><article data-type="fig" id="figobml366f69"><div id="ml366.f69" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701492.&p=BOOKS&id=189922_ml366f69.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f69.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701492." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701492</span></h3></div></article><article data-type="fig" id="figobml366f70"><div id="ml366.f70" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701492.&p=BOOKS&id=189922_ml366f70.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f70.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701492." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701492</span></h3><div class="caption"><p>MW = 297.35</p></div></div></article><article data-type="fig" id="figobml366f71"><div id="ml366.f71" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701484.&p=BOOKS&id=189922_ml366f71.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f71.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701484." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701484</span></h3></div></article><article data-type="fig" id="figobml366f72"><div id="ml366.f72" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701484.&p=BOOKS&id=189922_ml366f72.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f72.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701484." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701484</span></h3><div class="caption"><p>MW = 339.43</p></div></div></article><article data-type="fig" id="figobml366f73"><div id="ml366.f73" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=1H%20NMR%20Spectrum%20(300%20MHz%2C%20CDCl3)%20of%20Analog%20CID%2070701481.&p=BOOKS&id=189922_ml366f73.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f73.jpg" alt="1H NMR Spectrum (300 MHz, CDCl3) of Analog CID 70701481." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title"><sup>1</sup>H NMR Spectrum (300 MHz, CDCl<sub>3</sub>) of Analog CID 70701481</span></h3></div></article><article data-type="fig" id="figobml366f74"><div id="ml366.f74" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=UPLC-MS%20Chromatogram%20of%20Analog%20CID%2070701481.&p=BOOKS&id=189922_ml366f74.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK189922/bin/ml366f74.jpg" alt="UPLC-MS Chromatogram of Analog CID 70701481." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="title">UPLC-MS Chromatogram of Analog CID 70701481</span></h3><div class="caption"><p>MW = 286.33</p></div></div></article><article data-type="table-wrap" id="figobml366t15"><div id="ml366.t15" class="table"><h3><span class="label">Table H1</span><span class="title">Human kinase profiling results for ML366</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t15/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t15_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Kinase</th><th id="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a> @ 10 µM</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Abl</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">113</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ALK</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">111</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AMPKα1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">87</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ASK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">111</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Aurora-A</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">93</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CaMKI</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">93</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CDK1/cyclinB</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">102</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CDK2/cyclinA</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">116</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CDK6/cyclinD3</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">86</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CDK7/cyclinH/MAT1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">86</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CDK9/cyclin T1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">98</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CHK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">101</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CK1γ1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">62</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CK2α2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">89</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">c-RAF</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">102</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">DRAK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">97</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">eEF-2K</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">99</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">EGFR</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">EphA5</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">111</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">EphB4</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">90</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Fyn</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">107</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">GSK3β</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">84</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IGF-1R</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">125</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IKKα</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">111</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IRAK4</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">104</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">JAK2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">96</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">KDR</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">84</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">LOK</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">115</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Lyn</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">102</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MAPKAP-K2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">85</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MEK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">103</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MKK7β</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">109</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">91</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Mnk2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">95</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MSK2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">106</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MST1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">94</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">mTOR</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">71</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NEK2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">113</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">p70S6K</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">95</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PAK2</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PDGFRβ</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Pim-1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">105</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PKA</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">101</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PKBα</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">98</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PKCα</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PKCθ</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">94</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PKG1α</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">82</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Plk3</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">99</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PRAK</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">90</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ROCK-I</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">112</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Rse</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">84</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Rsk1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">109</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SAPK2a</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">114</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SRPK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">94</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TAK1</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">111</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PI3 Kinase (p110b/p85a)</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">96</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PI3 Kinase (p120g)</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">83</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PI3 Kinase (p110d/p85a)</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">80</td></tr><tr><td headers="hd_h_ml366.t15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PI3 Kinase (p110a/p85a)</td><td headers="hd_h_ml366.t15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">90</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml366t16"><div id="ml366.t16" class="table"><h3><span class="label">Table H2</span><span class="title">Radioligand binding assay results for ML366</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t16/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t16_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay</th><th id="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Species</th><th id="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Concentration (µM)</th><th id="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">% Inhibition</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adenosine A1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">22</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adenosine A2A</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">AdenosineA3</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">38</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic α1A</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-5</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic α1B</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-11</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic α1D</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic α2A</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic β1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adrenergic β2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">14</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Androgen (Testosterone) (AR)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bradykinin B1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bradykinin B2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium Channel L-Type, Benzothiazepine</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-2</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium Channel L-Type, Dihydropyridine</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcium Channel N-Type</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-2</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cannabinoid CB1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dopamine D1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dopamine D2S</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dopamine D3</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">17</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dopamine D4.2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">36</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Endothelin ETA</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Endothelin ETB</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Epidermal Growth Factor (EGF)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Estrogen ER alpha</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GABAA, Flunitrazepam, Central</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GABAA, Muscimol, Central</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">14</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GABA B1A</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glucocorticoid</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-7</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glutamate, Kainate</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glutamate, NMDA agonism</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glutamate, NMDA Glycine</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Glutamate, Phencyclidine</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Histamine H1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">17</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Histamine H2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Histamine H3</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Imidazoline, I2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-2</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interleukin, IL-1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">mouse</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Leukotriene, Cysteinyl, CysLT1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Melatonin MT1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">34</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Muscarinic M1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Muscarinic M2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Muscarinic M3</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-7</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neuropeptide Y1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neuropeptide Y2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nicotinic, Acetylcholine</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-6</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nicotinic, Acetylcholine α1, bungarotoxin</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-7</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Opiate δ1 (OP1, DOP)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Opiate, κ(OP2, KOP)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-8</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Opiate μ(OP3, MOP)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Phorbol Ester</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">mouse</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Platelet Activating Factor (PAF)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potassium Channel [KATP]</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">hamster</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potassium Channel hERG</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Prostanoid EP4</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-3</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purinergic P2X</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rabbit</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purinergic P2Y</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rolipram</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-13</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serotonin, (5-Hydroxytryptamine) 5-HT1A</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serotonin, (5-Hydroxytryptamine) 5-HT3</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-15</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sigma σ1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">43</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sodium channel, Site 2</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tachykinin NK1</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-6</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Thyroid hormone</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transporter, Dopamine (DAT)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transporter, GABA</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">rat</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transporter, Norepinephrine (NET)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13</td></tr><tr><td headers="hd_h_ml366.t16_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transporter, Serotonin (5-Hydroxytryptamine) (SERT)</td><td headers="hd_h_ml366.t16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">human</td><td headers="hd_h_ml366.t16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10</td><td headers="hd_h_ml366.t16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml366t18"><div id="ml366.t18" class="table"><h3><span class="label">Table A3</span><span class="title">Probe and Analog Information</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK189922/table/ml366.t18/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml366.t18_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD</th><th id="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</th><th id="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</th><th id="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">P/A<sup>†</sup></th><th id="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLSID</th><th id="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ML</th></tr></thead><tbody><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K53995654-001-07-6</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282758" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282758</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4443990</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">P</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820100</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML366[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML366</a></td></tr><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K73520786-001-01-2</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844167" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844167</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">70701501</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820105</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K36208737-001-01-0</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844166" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844166</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">70701486</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820106</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K40011623-001-01-9</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282753" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282753</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57525038</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820101</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K00837228-001-01-4</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/160844172" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">160844172</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">70701482</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820104</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ml366.t18_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BRD-K05519962-001-01-3</td><td headers="hd_h_ml366.t18_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/137282749" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">137282749</a></td><td headers="hd_h_ml366.t18_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">28938024</td><td headers="hd_h_ml366.t18_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A</td><td headers="hd_h_ml366.t18_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS004820099</td><td headers="hd_h_ml366.t18_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml366.tfn16"><p class="no_margin">A = analog; P = probe</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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