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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2 - 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="Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2">
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<meta name="citation_publisher" content="National Center for Biotechnology Information (US)">
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<meta name="citation_date" content="2010/09/02">
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<meta name="citation_author" content="Marion Lanier">
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<meta name="citation_author" content="John Cashman">
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<meta name="citation_author" content="Eduard Sergienko">
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<meta name="citation_author" content="Xochella Garcia">
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<meta name="citation_author" content="Brock Brown">
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<meta name="citation_author" content="Justin Rascon">
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<meta name="citation_author" content="Sonoko Narisawa">
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<meta name="citation_author" content="Ana Maria Simao">
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<meta name="citation_author" content="José Luis Millán">
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<meta name="citation_author" content="Derek Stonich">
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<meta name="citation_author" content="Ying Su">
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<meta name="citation_author" content="Russell Dahl">
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<meta name="citation_author" content="Thomas DY Chung">
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<meta name="citation_pmid" content="21433367">
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<meta name="DC.Title" content="Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2">
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<meta name="DC.Publisher" content="National Center for Biotechnology Information (US)">
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<meta name="DC.Contributor" content="Marion Lanier">
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<meta name="DC.Contributor" content="John Cashman">
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<meta name="DC.Contributor" content="Eduard Sergienko">
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<meta name="DC.Contributor" content="Xochella Garcia">
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<meta name="DC.Contributor" content="Brock Brown">
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<meta name="DC.Contributor" content="Justin Rascon">
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<meta name="DC.Contributor" content="Sonoko Narisawa">
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<meta name="DC.Contributor" content="Ana Maria Simao">
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<meta name="DC.Contributor" content="José Luis Millán">
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<meta name="DC.Contributor" content="Derek Stonich">
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<meta name="DC.Contributor" content="Ying Su">
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<meta name="DC.Contributor" content="Russell Dahl">
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<meta name="DC.Contributor" content="Thomas DY Chung">
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<meta name="DC.Date" content="2010/09/02">
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<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK47351/">
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<meta name="description" content="Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML095 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP.">
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<meta name="og:description" content="Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML095 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP.">
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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="_NBK47351_"><span class="title" itemprop="name">Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2</span></h1><p class="contribs">Lanier M, Cashman J, Sergienko E, et al.</p><p class="fm-aai"><a href="#_NBK47351_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>Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML095 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP.</p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> 1 R03 MH077602-01</p><p><b>Screening Center Name & PI:</b>
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<i>Conrad Prebys</i> Center for Chemical Genomics (<i>formerly Burnham Center for Chemical Genomics</i>) & Dr. John C. Reed</p><p><b>Chemistry Center Name & PI:</b>
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<i>Conrad Prebys</i> Center for Chemical Genomics (<i>formerly Burnham Center for Chemical Genomics)</i> & Dr. John C. Reed <i>(This series of compounds were developed with our collaborators at the Human Bimolecular Research Institute (HBRI) – Dr. Marion Lanier and Dr. John Cashman)</i></p><p><b>Assay Submitter & Institution:</b> Dr José Luis Millán & Sanford-Burnham Medical Research Institute (<i>formerly Burnham Institute for Medical Research</i>)</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1577</a></p><div id="ml095.s2"><h2 id="_ml095_s2_">Probe Structure & Characteristics</h2><div id="ml095.fu1" class="figure"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu1.jpg" alt="Image ml095fu1" /></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095tu1"><a href="/books/NBK47351/table/ml095.tu1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml095tu1" rid-ob="figobml095tu1"><img class="small-thumb" src="/books/NBK47351/table/ml095.tu1/?report=thumb" src-large="/books/NBK47351/table/ml095.tu1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml095.tu1"><a href="/books/NBK47351/table/ml095.tu1/?report=objectonly" target="object" rid-ob="figobml095tu1">Table</a></h4></div></div></div><div id="ml095.s3"><h2 id="_ml095_s3_">Recommendations for the scientific use of this probe</h2><p>Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function is still unknown (<a class="bibr" href="#ml095.r1" rid="ml095.r1">1</a>,<a class="bibr" href="#ml095.r2" rid="ml095.r2">2</a>) but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma (<a class="bibr" href="#ml095.r3" rid="ml095.r3">3</a>) and other cancers (<a class="bibr" href="#ml095.r4" rid="ml095.r4">4</a>). PLAP-specific inhibitors with selectivity over other tissue non-specific (<a class="bibr" href="#ml095.r5" rid="ml095.r5">5</a>) alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) can be used as tools to characterize the biological role of PLAP. The small molecule probe CID-25067483 will be useful to elucidate the key biological functions and natural substrates of human placental alkaline phosphatase (PLAP)</p></div><div id="ml095.s4"><h2 id="_ml095_s4_">1. Scientific Rationale for Project</h2><p>Alkaline phosphatases (EC 3.1.3.1) catalyze the hydrolysis of phosphomonoesters, releasing phosphate and alcohol. Alkaline phosphatases are dimeric enzymes found in most organisms. In human, four isozymes of alkaline phosphatases have been identified: three isozymes are tissue-specific and the fourth one is tissue-nonspecific. Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function is still unknown. However, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) will provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. Several amino acids (L-tryptophan, L-phenylalanine and L-leucine) and some other compounds (such as levamisole) inhibit PLAP and other APs with mM IC50 values. L-phenylalanylglycylglycine, the state of the art inhibitor of PLAP, is the only compound that demonstrates >10-fold selectivity to PLAP vs IAP or TNAP, yet its IC50 values in PLAP assays are 100–300 µM (<a class="bibr" href="#ml095.r6" rid="ml095.r6">6</a>).</p></div><div id="ml095.s5"><h2 id="_ml095_s5_">2. Project Description</h2><div id="ml095.s6"><h3>a. The original goal for probe characteristics</h3><p>This MLSCN carry-forward project was an early Cycle 2 assay proposal and a formal CPDP was not filed. It was derived based on work with tissue non-specific alkaline phosphatase inhibitors and later activator work, that suggested that PLAP specific inhibitors could also be useful tools for this class of isozyme with yet to be elucidated biological function.</p></div><div id="ml095.s7"><h3>b. Assay implementation and screening</h3><div id="ml095.s8"><h4>i. PubChem Bioassay Name(s), AID(s), Assay-Type (Primary, DR, Counterscreen, Secondary)</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095tu2"><a href="/books/NBK47351/table/ml095.tu2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml095tu2" rid-ob="figobml095tu2"><img class="small-thumb" src="/books/NBK47351/table/ml095.tu2/?report=thumb" src-large="/books/NBK47351/table/ml095.tu2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml095.tu2"><a href="/books/NBK47351/table/ml095.tu2/?report=objectonly" target="object" rid-ob="figobml095tu2">Table</a></h4></div></div><p>Primary assay details are described below.</p><p>PLAP screening was developed and done at the Burnham Center for Chemical Genomics (BCCG) within the Molecular Library Screening Center Network (MLSCN) as a selectivity screen for tissue nonspecific alkaline phosphatase (TNAP, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1056" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1056</a>). X01MH077602-01, Pharmacological inhibitors of tissue-nonspecific alkaline phosphatase (TNAP), Assay Provider Dr. José Luis Millán, Burnham Institute for Medical Research, La Jolla, CA.</p><div id="ml095.s9"><h5>Protocol</h5><div id="ml095.s10"><h5>PLAP assay materials</h5><ol><li class="half_rhythm"><div>PLAP protein was provided by Dr. José Luis Millán (Burnham Institute for Medical Research, San Diego, CA). The CDP-star was obtained from New England Biolabs.</div></li><li class="half_rhythm"><div>Assay Buffer: 250 mM DEA, pH 9.8, 2.5 mM MgCl<sub>2</sub>, and 0.05 mM ZnCl<sub>2</sub>.</div></li><li class="half_rhythm"><div>PLAP working solution contained a 1/6400 dilution in assay buffer. The solution was freshly prepared prior to use.</div></li><li class="half_rhythm"><div>CDP-star working solution contained 212.5 μM CDP-star in MQ water.</div></li><li class="half_rhythm"><div>TCEP working solution - 5 mM in 10% DMSO.</div></li></ol></div><div id="ml095.s11"><h5>PLAP HTS protocol</h5><ol><li class="half_rhythm"><div>4 μL of 100 μM compounds in 10% DMSO were dispensed in columns 3–24 of Greiner 384-well white small volume plates (784075).</div></li><li class="half_rhythm"><div>Using a Thermo WellMate dispenser 4 μL of the following solutions were added:</div><ol class="lower-alpha"><li class="half_rhythm"><div>TCEP working solution - column 1 (positive control).</div></li><li class="half_rhythm"><div>10% DMSO - column 2 (negative control).</div></li></ol></li><li class="half_rhythm"><div>8 μL of PLAP working solution was added to the whole plate using a WellMate bulk dispenser.</div></li><li class="half_rhythm"><div>8 μL of CDP-star working solution was added to the whole plate using WellMate bulk reagent dispenser.</div></li><li class="half_rhythm"><div>Final concentrations of the components in the assay were as follows:</div><ol class="lower-alpha"><li class="half_rhythm"><div>100 mM DEA, pH 9.8, 1.0 mM MgCl<sub>2</sub>, 0.02 mM ZnCl<sub>2</sub> (columns 1–24)</div></li><li class="half_rhythm"><div>1/16000 dilution PLAP (columns 1–24)</div></li><li class="half_rhythm"><div>85 μM CDP-star (columns 1–24)</div></li><li class="half_rhythm"><div>1 mM TCEP (columns 1)</div></li><li class="half_rhythm"><div>2 % DMSO (columns 1–24)</div></li><li class="half_rhythm"><div>20 μM compounds (columns 3–24)</div></li></ol></li><li class="half_rhythm"><div>Plates were incubated for 30 minutes at room temperature.</div></li><li class="half_rhythm"><div>Luminescence was measured on an Envision plate reader (Perkin Elmer).</div></li><li class="half_rhythm"><div>Data analysis was done using CBIS software (ChemInnovations, Inc).</div></li></ol></div></div><div id="ml095.s12"><h5>PLAP dose-response confirmation screening protocol</h5><ol><li class="half_rhythm"><div>Dose-response curves contained 10 concentrations of compounds obtained using 2-fold serial dilutions. Compounds were serially diluted in 100% DMSO, and diluted with water to 10% final DMSO concentration. 4 μL compounds in 10% DMSO were transferred into columns 3–22 of Greiner 384-well white small-volume plates (784075). Columns 1–2 and 23–24 contained 4 μL of TCEP working solution and 10% DMSO, respectively.</div></li><li class="half_rhythm"><div>8 μL of PLAP working solution was added to the whole plate using a WellMate bulk reagent dispenser (Matrix).</div></li><li class="half_rhythm"><div>8 μL of CDP-star working solution was added to the whole plate using a WellMate reagent bulk dispenser (Matrix).</div></li><li class="half_rhythm"><div>Plates were incubated for 30 min at room temperature.</div></li><li class="half_rhythm"><div>Luminescence was measured on an Envision plate reader (Perkin Elmer).</div></li><li class="half_rhythm"><div>Data analysis was performed using CBIS software (ChemInnovations, Inc) using a sigmoidal dose-response equation through non-linear regression</div></li></ol></div></div><div id="ml095.s13"><h4>ii. Assay Rationale & Description</h4><p>For the assay rationale, description, reagents and protocols, see <a href="#ml095.s6">section 2a</a> above.</p><p>For this screen 95,857 compounds were tested. The average Z’ for the assay was 0.69; the average signal to background was 38.6; the average signal to noise was 122.7 and the average signal window was 7.8. Initially 192 compounds were identified as primary positives with >= 50% inhibition of activity in the assay. After performing dose-response experiments with liquid DMSO stocks of these compounds, 82 of the hits generated dose-response curves.</p></div><div id="ml095.s14"><h4>iii. Summary of Results</h4><p>Primary hits from the PLAP HTS assay were confirmed and tested in parallel against TNAP for
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selectivity. A few hits were identified. There are many commercial analogues available and so
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Analogue-By-Catalogue (ABC) was performed in an iterative fashion. These were described in the
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initial probe report for PLAP focused on CID-665093. From the purchased compounds we were able to
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conclude that the dihydroxyl group of the catechol moiety were essential for inhibition of alkaline
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phosphatase activity. One of the series of molecules identified was compound <b>1,</b>
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CID-715454 (see <a class="figpopup" href="/books/NBK47351/figure/ml095.f1/?report=objectonly" target="object" rid-figpopup="figml095f1" rid-ob="figobml095f1">Figure 1</a>) This compound inhibited PLAP and TNAP with similar potency (1.9 and 7.2 µM, respectively) yet possessed significantly lower potency vs. IAP (50 µM). Interestingly, IAP and PLAP have much higher sequence similarity between themselves than with TNAP. Thus the above result suggested that additional compounds that are selective to PLAP are achievable.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml095f1" co-legend-rid="figlgndml095f1"><a href="/books/NBK47351/figure/ml095.f1/?report=objectonly" target="object" title="Figure 1" class="img_link icnblk_img figpopup" rid-figpopup="figml095f1" rid-ob="figobml095f1"><img class="small-thumb" src="/books/NBK47351/bin/ml095f1.gif" src-large="/books/NBK47351/bin/ml095f1.jpg" alt="Figure 1. Structure of the lead catechol MLS-0315687 (CID-715454) compound 1." /></a><div class="icnblk_cntnt" id="figlgndml095f1"><h4 id="ml095.f1"><a href="/books/NBK47351/figure/ml095.f1/?report=objectonly" target="object" rid-ob="figobml095f1">Figure 1</a></h4><p class="float-caption no_bottom_margin">Structure of the lead catechol MLS-0315687 (CID-715454) compound <i>1</i>. </p></div></div><p>Our collaborative partners at the Human BioMolecular Research Institute (<a href="http://www.hbri.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.hbri.org</a>) concentrated on developing the SAR of compound <b>1</b> (CID-715454) by synthesis of a series of compounds based on this scaffold.</p></div></div><div id="ml095.s15"><h3>c. Probe Optimization</h3><div id="ml095.s16"><h4>i. SAR & chemistry strategy that led to the probe</h4><p>The SAR was developed primarily by the targeted synthesis to improve selectivity against TNAP and IAP while maintaining the potency against PLAP. The objective of the hit-to-lead refinement chemistry was to develop a tractable route for the synthesis of probe candidates, prepare authentic samples, confirm structure and purity, and provide enough material for submission to the MLSMR. <a class="figpopup" href="/books/NBK47351/figure/ml095.f2/?report=objectonly" target="object" rid-figpopup="figml095f2" rid-ob="figobml095f2">Figure 2</a> below summarizes the points of variation of the series. All three regions of the lead were explored: left hand side (LHS), Linker and right hand side (RHS).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml095f2" co-legend-rid="figlgndml095f2"><a href="/books/NBK47351/figure/ml095.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml095f2" rid-ob="figobml095f2"><img class="small-thumb" src="/books/NBK47351/bin/ml095f2.gif" src-large="/books/NBK47351/bin/ml095f2.jpg" alt="Figure 2. Probe analogs variations: 3 regions were explored by chemical synthesis: the left hand side (LHS), linker and right hand side (RHS)." /></a><div class="icnblk_cntnt" id="figlgndml095f2"><h4 id="ml095.f2"><a href="/books/NBK47351/figure/ml095.f2/?report=objectonly" target="object" rid-ob="figobml095f2">Figure 2</a></h4><p class="float-caption no_bottom_margin">Probe analogs variations: 3 regions were explored by chemical synthesis: the left hand side (LHS), linker and right hand side (RHS). </p></div></div><div id="ml095.s17"><h5>Establishing an SAR</h5><p>A library of 34 compounds was synthesized according to the procedures illustrated in <a class="figpopup" href="/books/NBK47351/figure/ml095.f5/?report=objectonly" target="object" rid-figpopup="figml095f5" rid-ob="figobml095f5">Scheme 2</a>, below. Compounds were compared to CID-715454 (MLS-0315687) in the different bioassays (PLAP, TNAP and IAP in some cases). Three main areas of the lead structure were examined for the SAR (<a class="figpopup" href="/books/NBK47351/figure/ml095.f2/?report=objectonly" target="object" rid-figpopup="figml095f2" rid-ob="figobml095f2">Figure 2</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml095f5" co-legend-rid="figlgndml095f5"><a href="/books/NBK47351/figure/ml095.f5/?report=objectonly" target="object" title="Scheme 2" class="img_link icnblk_img figpopup" rid-figpopup="figml095f5" rid-ob="figobml095f5"><img class="small-thumb" src="/books/NBK47351/bin/ml095f5.gif" src-large="/books/NBK47351/bin/ml095f5.jpg" alt="Scheme 2. Synthesis of analogs of lead structure CID-715454 (MLS-0315687)." /></a><div class="icnblk_cntnt" id="figlgndml095f5"><h4 id="ml095.f5"><a href="/books/NBK47351/figure/ml095.f5/?report=objectonly" target="object" rid-ob="figobml095f5">Scheme 2</a></h4><p class="float-caption no_bottom_margin">Synthesis of analogs of lead structure CID-715454 (MLS-0315687). </p></div></div><p>Chemical re-synthesis of CID-715454 (MLS-0315687) was done to compare an authentic sample with the commercially purchased compound in the bioassays used. Exploration of the left hand side of the molecule (<a class="figpopup" href="/books/NBK47351/table/ml095.t5/?report=objectonly" target="object" rid-figpopup="figml095t5" rid-ob="figobml095t5">Table 5</a>) showed that the 3,4-dihydroxy phenyl was crucial for functional inhibitory activity. Removing one the hydroxyl groups, CID-25067456 (MLS-0315814) and CID-25199542 (MLS-0390951), or capping one or both hydroxyl groups, CID-25067475, CID-25067473 and CID-694596 (MLS-0315844, MLS-0315843, MLS-0315815, respectively) led to inactive compounds. Replacing the 3,4-dihydroxyphenyl by a 2,4-dichloro-phenyl substitution, CID-974963 (MLS-0390949) that is a favored feature for TNAP inhibitory activity in other series <sup>5</sup> afforded an inactive compound.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095t5"><a href="/books/NBK47351/table/ml095.t5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figml095t5" rid-ob="figobml095t5"><img class="small-thumb" src="/books/NBK47351/table/ml095.t5/?report=thumb" src-large="/books/NBK47351/table/ml095.t5/?report=previmg" alt="Table 5. Exploration of the left hand side of the lead structure." /></a><div class="icnblk_cntnt"><h4 id="ml095.t5"><a href="/books/NBK47351/table/ml095.t5/?report=objectonly" target="object" rid-ob="figobml095t5">Table 5</a></h4><p class="float-caption no_bottom_margin">Exploration of the left hand side of the lead structure. </p></div></div><p>A small survey of the linker region was done and we observed that any substitution tried led to significant deterioration of inhibitory activity (<a class="figpopup" href="/books/NBK47351/table/ml095.t6/?report=objectonly" target="object" rid-figpopup="figml095t6" rid-ob="figobml095t6">Table 6</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095t6"><a href="/books/NBK47351/table/ml095.t6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figml095t6" rid-ob="figobml095t6"><img class="small-thumb" src="/books/NBK47351/table/ml095.t6/?report=thumb" src-large="/books/NBK47351/table/ml095.t6/?report=previmg" alt="Table 6. Exploration of the linker." /></a><div class="icnblk_cntnt"><h4 id="ml095.t6"><a href="/books/NBK47351/table/ml095.t6/?report=objectonly" target="object" rid-ob="figobml095t6">Table 6</a></h4><p class="float-caption no_bottom_margin">Exploration of the linker. </p></div></div><p>Exploration of the RHS of the molecule was done using preliminary data generated from the PLAP HTS assay as well as newly synthesized compounds. Compound CID-715454 (MLS-0315678) and other alkyl-substituted analogs (CID-25067503 (MLS-0315858), not shown) suggested that an aromatic ring was necessary for activity. HTS assay results showed also, that all the catechol compounds active carried various heteroaromatic rings, mostly linked through a sulfur atom and were weakly or non selective for TNAP [<a class="figpopup" href="/books/NBK47351/table/ml095.t7/?report=objectonly" target="object" rid-figpopup="figml095t7" rid-ob="figobml095t7">Table 7</a>, compounds CID-586278, -1515366, and -2940433 (MLS-0051931, 0008112, 0077534, respectively)]. Exploring the RHS region with heterocycles such as imidazoles, triazoles and pyrazoles directly attached to the core led to compounds active vs. PLAP and selective over TNAP, CID-25067472, -25067487, -747227 (MLS-0315813, 0315850, 0390948, respectively). A more thorough exploration followed using the imidazole ring.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095t7"><a href="/books/NBK47351/table/ml095.t7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figml095t7" rid-ob="figobml095t7"><img class="small-thumb" src="/books/NBK47351/table/ml095.t7/?report=thumb" src-large="/books/NBK47351/table/ml095.t7/?report=previmg" alt="Table 7. Exploration of the right hand side of the lead structure." /></a><div class="icnblk_cntnt"><h4 id="ml095.t7"><a href="/books/NBK47351/table/ml095.t7/?report=objectonly" target="object" rid-ob="figobml095t7">Table 7</a></h4><p class="float-caption no_bottom_margin">Exploration of the right hand side of the lead structure. </p></div></div><p>A small library of substituents to explore the inhibitory potency around the imidazole moiety was prepared and tested against PLAP, TNAP and IAP. The results are summarized in <a class="figpopup" href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object" rid-figpopup="figml095t8" rid-ob="figobml095t8">Table 8</a>. Significantly, utilization of imidazole core provided improved selectivity vs. TNAP yet decreased selectivity vs. IAP. The presence of a hydrogen or small alkyl (methyl, ethyl) at the 2-position (R7) had little influence on TNAP inhibitory activity. With the introduction of a bulkier group at the 2-position such as a phenyl, CID-25067481 (MLS-0315847), inhibition activity decreased (IC<sub>50</sub>=17.2 µM). At the 4 and 5 positions (R8) of the imidazole group, a small group (methyl), CID-25199538 (MLS-0390945), maintained activity compared to the unsubstantiated imidazole. A larger group such as bromine, CID-2506747 (MLS-0315846), led to a decrease in activity by about 7-fold. Adding a 2-methyl substituent to the broom compound had an additive effect and the activity of CID-25067477 (MLS-0315845) decreased to 4.96 µM with concomitant loss of selectivity vs. TNAP. Interestingly, an unsubstituted benzimidazole CID-25067493 (MLS-0315853) was tolerated and more potent than the unsubstituted imidazole (IC50 = 1.53 µM and 3.2 µM respectively) but was also less selective vs. TNAP.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095t8"><a href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img figpopup" rid-figpopup="figml095t8" rid-ob="figobml095t8"><img class="small-thumb" src="/books/NBK47351/table/ml095.t8/?report=thumb" src-large="/books/NBK47351/table/ml095.t8/?report=previmg" alt="Table 8. Exploration around MLS-0615813." /></a><div class="icnblk_cntnt"><h4 id="ml095.t8"><a href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object" rid-ob="figobml095t8">Table 8</a></h4><p class="float-caption no_bottom_margin">Exploration around MLS-0615813. </p></div></div></div><div id="ml095.s18"><h5>Selectivity over TNAP</h5><p>The most interesting results for this series of imidazoles were the selectivity inhibition of PLAP compared with TNAP and IAP. Results are summarized in <a class="figpopup" href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object" rid-figpopup="figml095t8" rid-ob="figobml095t8">Table 8</a>. While substitution at the 2 position of the imidazole (R7) allowed to maintain the selectivity over TNAP, CID-25067472 (MLS-0315813) IC<sub>50</sub>>100 µM, CID-25067491 (MLS-0315852) IC<sub>50</sub>>100 µM, CID-25067483 (MLS-0315848) IC<sub>50</sub>=59.6 µM, CID-25067481 (MLS-0315847) IC<sub>50</sub>>100 µM, substitution at the 4 position (R8) resulted in significant loss of selectivity over TNAP. The presence of a benzimidazole instead of an imidazole led to a compound with an IC<sub>50</sub> below 15 µM for TNAP. In summary, varying the R8 GROUP can control selectivity over TNAP. When R8 is hydrogen, the compound showed no activity for TNAP CID-25067493 (MLS-0315813). R7 had a weak influence on TNAP selectivity.</p></div><div id="ml095.s19"><h5>Selectivity over IAP</h5><p>The 7 best compounds in the PLAP assay were also tested in the IAP assay. Results are summarized in <a class="figpopup" href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object" rid-figpopup="figml095t8" rid-ob="figobml095t8">Table 8</a>. An early trend appears to show that the R7 position was critical for IAP selectivity. When the R7 substituent volume increased from hydrogen to methyl to ethyl, the IC<sub>50</sub> in the IAP assay increased and led to inactive compounds (IC<sub>50</sub> = 22.4 µM, 64.6 µM, >100 µM respectively). Similarly, in the two benzimidazoles, CID-25067493 (MLS-0315853) and CID-25067495 (MLS-0315854) methyl group at R7 position led to >7-fold increase in selectivity vs. IAP.</p><p>In summary, we have been able to develop a series of imidazole and pyrazolo catechols that maintained inhibitory activity of the original screening hit CID-715454 (MLS-0315687) vs. PLAP while generating selectivity over the 2 isozymes, TNAP and IAP, and further differential selectivity between these two latter isozymes.</p><div id="ml095.fu2" class="figure"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu35.jpg" alt="Image ml095fu35" /></div></div></div></div></div></div><div id="ml095.s20"><h2 id="_ml095_s20_">3. Probe</h2><div id="ml095.s21"><h3>a. Chemical name</h3><p>1-(3,4-dihydroxyphenyl)-2-(2-ethylimidazol-1-yl)ethanone hydrochloride <b>[<a href="/pcsubstance/?term=ML095[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML095</a>]</b></p></div><div id="ml095.s22"><h3>b. Probe chemical structure</h3><div id="ml095.f3" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47351/bin/ml095f3.jpg" alt="Figure 3. Structure of probe compound MLS-0315848 (CID-25067483)." /></div><h3><span class="label">Figure 3</span><span class="title">Structure of probe compound MLS-0315848 (CID-25067483)</span></h3></div></div><div id="ml095.s23"><h3>c. Structural Verification Information of probe SID</h3><p><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405584</a>. Spectral data supporting proposed structure:</p><p><sup>1</sup>H NMR (300 MHz, CD3OD) δ: 1.29 (t, <i>J</i> = 7.7MHz, 3H), 2.76 (q, <i>J</i> = 7.7MHz, 2H), 4.8 (s, 2H), 6.83 (d, <i>J</i> = 8.4MHz, 1H), 6.99 (s, 2H), 7.42 (s, 1H), 7.43 (d, J = 6.6MHz 1H).</p><div id="ml095.fu3" class="figure"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu36.jpg" alt="Image ml095fu36" /></div></div><div id="ml095.fu4" class="figure"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu37.jpg" alt="Image ml095fu37" /></div></div><div id="ml095.fu5" class="figure"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu38.jpg" alt="Image ml095fu38" /></div></div></div><div id="ml095.s24"><h3>d. PubChem CID (corresponding to the SID)</h3><p>CID-25067483</p></div><div id="ml095.s25"><h3>e. Availability from a vendor</h3><p>Not a commercial source</p></div><div id="ml095.s26"><h3>f. MLS#'s of probe molecule and five related samples that were submitted to the SMR collection</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095t4"><a href="/books/NBK47351/table/ml095.t4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml095t4" rid-ob="figobml095t4"><img class="small-thumb" src="/books/NBK47351/table/ml095.t4/?report=thumb" src-large="/books/NBK47351/table/ml095.t4/?report=previmg" alt="Table 4. Submission information on Probe and analogs." /></a><div class="icnblk_cntnt"><h4 id="ml095.t4"><a href="/books/NBK47351/table/ml095.t4/?report=objectonly" target="object" rid-ob="figobml095t4">Table 4</a></h4><p class="float-caption no_bottom_margin">Submission information on Probe and analogs. </p></div></div></div><div id="ml095.s27"><h3>g. Mode of action for biological activity of probe</h3><p>The probe is a biochemical inhibitor of PLAP. The mode of action for the biological activity of this probe has not yet been elucidated.</p></div><div id="ml095.s28"><h3>h. Detailed synthetic pathway for making probe</h3><div id="ml095.f4" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47351/bin/ml095f4.jpg" alt="Scheme 1. Synthesis of MLS-0315848 (CID-25067483)." /></div><h3><span class="label">Scheme 1</span><span class="title">Synthesis of MLS-0315848 (CID-25067483)</span></h3></div><p>To 50 mg (0.27 mmol, Aldrich) of 2-chloro-3’,4’-dihydroxyacetophenone in 1 mL dioxane was added 26 mg (0.27 mmol, TCI) of 2-ethylimidazole. The solution was stirred overnight in a sealed vial at room temperature. The reaction was checked by TLC for completion (dichloromethane/methanol, 90:10, v/v). The reaction product precipitated out of solution. The precipitate was filtered, washed with a minimum amount of dioxane then dried under high vacuum to afford 35 mg of the probe as a beige solid.</p><p><sup>1</sup>H NMR (300 MHz, CD<sub>3</sub>OD) δ: 1.29 (t, <i>J</i> = 7.7MHz, 3H), 2.76 (q, <i>J</i> = 7.7MHz, 2H), 4.8 (s, 2H), 6.83 (d, <i>J</i> = 8.4MHz, 1H), 6.99 (s, 2H), 7.42 (s, 1H), 7.43 (d, J = 6.6MHz 1H). MS (ESI) C<sub>13</sub>H<sub>14</sub>N<sub>2</sub>O<sub>3</sub>, <i>m/z</i> = 246.1, found <i>m/z</i> = 247.27 [M+H].</p><p>See spectra above in <a href="#ml095.s23">Sec. 3.c. “Structural Verification Information of Probe SID</a>.</p></div><div id="ml095.s29"><h3>i. Summary of probe properties (solubility, absorbance/fluorescence, reactivity, toxicity, etc.)</h3><p>Probe compounds is soluble in dimethylsulfoxide at 20 mg/ml.</p></div><div id="ml095.s30"><h3>j. Properties Computed from Structure</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml095tu3"><a href="/books/NBK47351/table/ml095.tu3/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml095tu3" rid-ob="figobml095tu3"><img class="small-thumb" src="/books/NBK47351/table/ml095.tu3/?report=thumb" src-large="/books/NBK47351/table/ml095.tu3/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml095.tu3"><a href="/books/NBK47351/table/ml095.tu3/?report=objectonly" target="object" rid-ob="figobml095tu3">Table</a></h4></div></div></div></div><div id="ml095.s31"><h2 id="_ml095_s31_">4. Bibliography</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ml095.r1">Hoylaerts MF, Manes T, Millán JL. Molecular mechanism of uncompetitive inhibition of human placental and germ-cell alkaline phosphatase. <span><span class="ref-journal">Biochem J. </span>1992;<span class="ref-vol">286</span>(Pt 1):23–30.</span> [<a href="/pmc/articles/PMC1133013/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1133013</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1520273" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1520273</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ml095.r2">Wennberg C, Kozlenkov A, Di
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Mauro S, Fröhlander N, Beckman L, Hoylaerts MF, Millán JL. Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP). <span><span class="ref-journal">Human Mutation. </span>2002;<span class="ref-vol">19</span>(3):258–267.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11857742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11857742</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ml095.r3">Wahren B, Hinkula J, Stigbrand T, Jeppsson A, Andersson L, Esposti PL, Edsmyr F, Millán JL. Phenotypes of placental-type alkaline phosphatase in seminoma sera. <span><span class="ref-journal">Int J of Cancer. </span>2006;<span class="ref-vol">37</span>(4):595–600.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3957465" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3957465</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ml095.r4">Fishman WH. Clinical and biological significance of an isozyme tumor marker—PLAP. <span><span class="ref-journal">Clin Biochem . </span>1987;<span class="ref-vol">20</span>:387–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3325192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3325192</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ml095.r5">Sidique S, Ardecky R, Su Y, Narisawa S, Brown B, Millán JL, Sergienko E, Cosford NDP. Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). <span><span class="ref-journal">Bioorg Med Chem Lett. </span>2009;<span class="ref-vol">19</span>:222–225.</span> [<a href="/pmc/articles/PMC2752324/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2752324</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19038545" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19038545</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ml095.r6">Goldstein DJ, Rogers C, Harris H. Evolution of alkaline phosphatases in primates. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>1982;<span class="ref-vol">19</span>:879–883.</span> [<a href="/pmc/articles/PMC345856/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC345856</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/6950431" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6950431</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK47351_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Marion Lanier</span>, <span itemprop="author">John Cashman</span>, <span itemprop="author">Eduard Sergienko</span>, <span itemprop="author">Xochella Garcia</span>, <span itemprop="author">Brock Brown</span>, <span itemprop="author">Justin Rascon</span>, <span itemprop="author">Sonoko Narisawa</span>, <span itemprop="author">Ana Maria Simao</span>, <span itemprop="author">José Luis Millán</span>, <span itemprop="author">Derek Stonich</span>, <span itemprop="author">Ying Su</span>, <span itemprop="author">Russell Dahl</span>, and <span itemprop="author">Thomas DY Chung</span>.</p><h3>Publication History</h3><p class="small">Received: <span itemprop="datePublished">May 16, 2009</span>; Last Update: <span itemprop="dateModified">September 2, 2010</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>Lanier M, Cashman J, Sergienko E, et al. Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2. 2009 May 16 [Updated 2010 Sep 2]. 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/ml096/?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/ml090/?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="figobml095fu1"><div id="ml095.fu1" class="figure"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095fu1.jpg" alt="Image ml095fu1" /></div></div></article><article data-type="table-wrap" id="figobml095tu1"><div id="ml095.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml095.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID/ML</th><th id="hd_h_ml095.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Target Name</th><th id="hd_h_ml095.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC50/EC50 (nM) [SID, AID]</th><th id="hd_h_ml095.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Anti-target Name(s)</th><th id="hd_h_ml095.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC50/EC50 (μM) [SID, AID]</th><th id="hd_h_ml095.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Selectivity</th><th id="hd_h_ml095.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Secondary Assay(s) Name: IC50/EC50 (nM) [SID, AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml095.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067483<br /><br />
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<a href="/pcsubstance/?term=ML095[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML095</a></td><td headers="hd_h_ml095.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PLAP</td><td headers="hd_h_ml095.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4,240 nM IC<sub>50</sub><br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405584</a><br />
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1512" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1512</a></td><td headers="hd_h_ml095.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TNAP</td><td headers="hd_h_ml095.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100 µM IC<sub>50</sub><br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405584</a><br /><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1056" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1056</a></td><td headers="hd_h_ml095.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">> 27</td><td headers="hd_h_ml095.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ml095.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ml095.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IAP</td><td headers="hd_h_ml095.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100 µM IC<sub>50</sub><br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405584</a><br /><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1017" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1017</a></td><td headers="hd_h_ml095.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">> 27</td><td headers="hd_h_ml095.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml095tu2"><div id="ml095.tu2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.tu2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.tu2_lrgtbl__"><table><thead><tr><th id="hd_h_ml095.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PubChem BioAssay Name</th><th id="hd_h_ml095.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AIDs</th><th id="hd_h_ml095.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe Type</th><th id="hd_h_ml095.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Type</th><th id="hd_h_ml095.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Format</th><th id="hd_h_ml095.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Detection & well format</th></tr></thead><tbody><tr><td headers="hd_h_ml095.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Luminescent assay for HTS discovery of chemical inhibitors of placental alkaline phosphatase</td><td headers="hd_h_ml095.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/690" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">690</a></td><td headers="hd_h_ml095.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml095.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml095.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml095.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (1536)</td></tr><tr><td headers="hd_h_ml095.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Luminescent assay for HTS discovery of chemical inhibitors of placental alkaline phosphatase confirmation</td><td headers="hd_h_ml095.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1512" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1512</a></td><td headers="hd_h_ml095.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml095.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmatory</td><td headers="hd_h_ml095.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml095.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (384)</td></tr><tr><td headers="hd_h_ml095.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In Vitro TNAP Dose Response<br /> Luminescent Assay for SAR Study</td><td headers="hd_h_ml095.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1056" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1056</a></td><td headers="hd_h_ml095.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml095.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary Assay for specificity</td><td headers="hd_h_ml095.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml095.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (384)</td></tr><tr><td headers="hd_h_ml095.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Luminescent assay for identification of inhibitors of human intestinal alkaline phosphatase [Confirmatory]</td><td headers="hd_h_ml095.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1017" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1017</a></td><td headers="hd_h_ml095.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml095.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreen Assay for specificity</td><td headers="hd_h_ml095.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml095.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (1536)</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml095f1"><div id="ml095.f1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095f1.jpg" alt="Figure 1. Structure of the lead catechol MLS-0315687 (CID-715454) compound 1." /></div><h3><span class="label">Figure 1</span><span class="title">Structure of the lead catechol MLS-0315687 (CID-715454) compound <b>1</b></span></h3></div></article><article data-type="fig" id="figobml095f2"><div id="ml095.f2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095f2.jpg" alt="Figure 2. Probe analogs variations: 3 regions were explored by chemical synthesis: the left hand side (LHS), linker and right hand side (RHS)." /></div><h3><span class="label">Figure 2</span><span class="title">Probe analogs variations: 3 regions were explored by chemical synthesis: the left hand side (LHS), linker and right hand side (RHS)</span></h3></div></article><article data-type="fig" id="figobml095f5"><div id="ml095.f5" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095f5.jpg" alt="Scheme 2. Synthesis of analogs of lead structure CID-715454 (MLS-0315687)." /></div><h3><span class="label">Scheme 2</span><span class="title">Synthesis of analogs of lead structure CID-715454 (MLS-0315687)</span></h3></div></article><article data-type="table-wrap" id="figobml095t5"><div id="ml095.t5" class="table"><h3><span class="label">Table 5</span><span class="title">Exploration of the left hand side of the lead structure</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.t5_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml095.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu2.jpg" alt="Image ml095fu2.jpg" /></div></th><th id="hd_h_ml095.t5_1_1_1_2" colspan="7" rowspan="1" style="text-align:left;vertical-align:top;"></th></tr><tr><th headers="hd_h_ml095.t5_1_1_1_1" id="hd_h_ml095.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">R4</th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu3.jpg" alt="Image ml095fu3.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu4.jpg" alt="Image ml095fu4.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu5.jpg" alt="Image ml095fu5.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu6.jpg" alt="Image ml095fu6.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu7.jpg" alt="Image ml095fu7.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu8.jpg" alt="Image ml095fu8.jpg" /></div></th><th headers="hd_h_ml095.t5_1_1_1_2" id="hd_h_ml095.t5_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu9.jpg" alt="Image ml095fu9.jpg" /></div></th></tr></thead><tbody><tr><td headers="hd_h_ml095.t5_1_1_1_1 hd_h_ml095.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-#</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0315687</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0315814</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0390951</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0315844</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0315843</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0315815</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0390949</td></tr><tr><td headers="hd_h_ml095.t5_1_1_1_1 hd_h_ml095.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-715454</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25067456</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25199542</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25067475</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25067473</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-694596</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-974963</td></tr><tr><td headers="hd_h_ml095.t5_1_1_1_1 hd_h_ml095.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SID</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405531" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405531</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405532" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405532</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309188" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309188</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405580" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405580</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405579" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405579</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405533" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405533</a></td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309186" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309186</a></td></tr><tr><td headers="hd_h_ml095.t5_1_1_1_1 hd_h_ml095.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PLAP activity (IC<sub>50</sub>)</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.21µM</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml095.t5_1_1_1_2 hd_h_ml095.t5_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml095t6"><div id="ml095.t6" class="table"><h3><span class="label">Table 6</span><span class="title">Exploration of the linker</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.t6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.t6_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml095.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Structure</th><th id="hd_h_ml095.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu10.jpg" alt="Image ml095fu10.jpg" /></div></th><th id="hd_h_ml095.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu11.jpg" alt="Image ml095fu11.jpg" /></div></th><th id="hd_h_ml095.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu12.jpg" alt="Image ml095fu12.jpg" /></div></th></tr></thead><tbody><tr><td headers="hd_h_ml095.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-#</td><td headers="hd_h_ml095.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0390944</td><td headers="hd_h_ml095.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0390952</td><td headers="hd_h_ml095.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0390954</td></tr><tr><td headers="hd_h_ml095.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID</td><td headers="hd_h_ml095.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25199537</td><td headers="hd_h_ml095.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25199543</td><td headers="hd_h_ml095.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25199545</td></tr><tr><td headers="hd_h_ml095.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SID</td><td headers="hd_h_ml095.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309181" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309181</a></td><td headers="hd_h_ml095.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309189" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309189</a></td><td headers="hd_h_ml095.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309191" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309191</a></td></tr><tr><td headers="hd_h_ml095.t6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PLAP inhibition (IC<sub>50</sub>)</td><td headers="hd_h_ml095.t6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.2µM</td><td headers="hd_h_ml095.t6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.7</td><td headers="hd_h_ml095.t6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml095t7"><div id="ml095.t7" class="table"><h3><span class="label">Table 7</span><span class="title">Exploration of the right hand side of the lead structure</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.t7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.t7_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml095.t7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu13.jpg" alt="Image ml095fu13.jpg" /></div></th><th id="hd_h_ml095.t7_1_1_1_2" colspan="7" rowspan="1" style="text-align:left;vertical-align:top;"></th></tr><tr><th headers="hd_h_ml095.t7_1_1_1_1" id="hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">R5</th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu14.jpg" alt="Image ml095fu14.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu15.jpg" alt="Image ml095fu15.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu16.jpg" alt="Image ml095fu16.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu17.jpg" alt="Image ml095fu17.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu18.jpg" alt="Image ml095fu18.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu19.jpg" alt="Image ml095fu19.jpg" /></div></th><th headers="hd_h_ml095.t7_1_1_1_2" id="hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu20.jpg" alt="Image ml095fu20.jpg" /></div></th></tr></thead><tbody><tr><td headers="hd_h_ml095.t7_1_1_1_1 hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-#</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0315678</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0051931</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0008112</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0077534</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0315813</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0315850</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS-0390948</td></tr><tr><td headers="hd_h_ml095.t7_1_1_1_1 hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-2830496</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-586278</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-1515366</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-2940433</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25067472</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-25067487</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CID-747227</td></tr><tr><td headers="hd_h_ml095.t7_1_1_1_1 hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SID</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373922" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373922</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373536" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373536</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373572" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373572</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373574" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373574</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405578</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405586" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405586</a></td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309185" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57309185</a></td></tr><tr><td headers="hd_h_ml095.t7_1_1_1_1 hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PLAP inhibition (IC<sub>50</sub>)</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.16µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.97µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.95µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.11µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.4µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.65 µM</td></tr><tr><td headers="hd_h_ml095.t7_1_1_1_1 hd_h_ml095.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TNAP inhibition (IC<sub>50</sub>)</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.82µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.04µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.2µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100µM</td><td headers="hd_h_ml095.t7_1_1_1_2 hd_h_ml095.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">75.7 µM</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml095t8"><div id="ml095.t8" class="table"><h3><span class="label">Table 8</span><span class="title">Exploration around MLS-0615813</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.t8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.t8_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml095.t8_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu21.jpg" alt="Image ml095fu21.jpg" /></div></th><th id="hd_h_ml095.t8_1_1_1_2" colspan="4" rowspan="1" style="text-align:center;vertical-align:top;"></th></tr><tr><th headers="hd_h_ml095.t8_1_1_1_1" id="hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu22.jpg" alt="Image ml095fu22.jpg" /></div></th><th headers="hd_h_ml095.t8_1_1_1_2" id="hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu23.jpg" alt="Image ml095fu23.jpg" /></div></th><th headers="hd_h_ml095.t8_1_1_1_2" id="hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu24.jpg" alt="Image ml095fu24.jpg" /></div></th><th headers="hd_h_ml095.t8_1_1_1_2" id="hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu25.jpg" alt="Image ml095fu25.jpg" /></div></th><th headers="hd_h_ml095.t8_1_1_1_2" id="hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu26.jpg" alt="Image ml095fu26.jpg" /></div></th></tr></thead><tbody><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-#</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315813</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315852</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315848</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315847</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067472</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067491</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067483</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067481</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405578</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405588" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405588</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405584</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405583" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405583</a></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PLAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.11</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.37</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.73</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">17.2</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TNAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">59.6</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18.5</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">64.6</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">nd</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu27.jpg" alt="Image ml095fu27.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu28.jpg" alt="Image ml095fu28.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu29.jpg" alt="Image ml095fu29.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu30.jpg" alt="Image ml095fu30.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu31.jpg" alt="Image ml095fu31.jpg" /></div></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-#</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315855</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315846</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315853</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315851</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067497</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067479</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067493</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067489</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405591" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405591</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405582" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405582</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405589" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405589</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405587" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405587</a></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PLAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.81</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.8</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.53</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.83</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TNAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">41.1</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">47.5</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">14</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">nd</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">nd</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">14.8</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">nd</td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu32.jpg" alt="Image ml095fu32.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu33.jpg" alt="Image ml095fu33.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47351/bin/ml095fu34.jpg" alt="Image ml095fu34.jpg" /></div></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS #</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315845</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315854</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PLAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.96</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.51</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067477</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-25067495</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405581" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405581</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56405590</a></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TNAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.74</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.2</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml095.t8_1_1_1_1 hd_h_ml095.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IAP IC<sub>50</sub> (µM)</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">nd</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml095.t8_1_1_1_2 hd_h_ml095.t8_1_1_2_5" 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="ml095.tfn1"><p class="no_margin">nd: not determined</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml095fu2"><div id="ml095.fu2" class="figure"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095fu35.jpg" alt="Image ml095fu35" /></div></div></article><article data-type="fig" id="figobml095f3"><div id="ml095.f3" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095f3.jpg" alt="Figure 3. Structure of probe compound MLS-0315848 (CID-25067483)." /></div><h3><span class="label">Figure 3</span><span class="title">Structure of probe compound MLS-0315848 (CID-25067483)</span></h3></div></article><article data-type="fig" id="figobml095fu3"><div id="ml095.fu3" class="figure"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095fu36.jpg" alt="Image ml095fu36" /></div></div></article><article data-type="fig" id="figobml095fu4"><div id="ml095.fu4" class="figure"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095fu37.jpg" alt="Image ml095fu37" /></div></div></article><article data-type="fig" id="figobml095fu5"><div id="ml095.fu5" class="figure"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095fu38.jpg" alt="Image ml095fu38" /></div></div></article><article data-type="table-wrap" id="figobml095t4"><div id="ml095.t4" class="table"><h3><span class="label">Table 4</span><span class="title">Submission information on Probe and analogs</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.t4_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe /Analog</th><th id="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-# (BCCG#)</th><th id="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</th><th id="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</th><th id="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Source (vendor or BCCG syn)</th><th id="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Amt (mg)</th><th id="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Source Lot</th></tr></thead><tbody><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0315848</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25067483</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56405584</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-MLG-I-126D</td></tr><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 1</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0315687</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715454</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405531" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56405531</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-100206</td></tr><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 2</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390945</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25199538</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57309182" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57309182</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-MLG-I-182A</td></tr><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 3</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0315854</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25067495</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56405590</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-MLG-I-128B</td></tr><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 4</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0315852</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25067491</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405588" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56405588</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-MLG-I-126</td></tr><tr><td headers="hd_h_ml095.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 5</td><td headers="hd_h_ml095.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0315813</td><td headers="hd_h_ml095.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25067472</td><td headers="hd_h_ml095.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56405578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56405578</a></td><td headers="hd_h_ml095.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI syn</td><td headers="hd_h_ml095.t4_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml095.t4_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">HBRI-100205</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml095f4"><div id="ml095.f4" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47351/bin/ml095f4.jpg" alt="Scheme 1. Synthesis of MLS-0315848 (CID-25067483)." /></div><h3><span class="label">Scheme 1</span><span class="title">Synthesis of MLS-0315848 (CID-25067483)</span></h3></div></article><article data-type="table-wrap" id="figobml095tu3"><div id="ml095.tu3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47351/table/ml095.tu3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml095.tu3_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Molecular Weight</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">282.7228 [g/mol]</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Molecular Formula</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">C13H15ClN2O3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">H-Bond Donor</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">H-Bond Acceptor</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rotatable Bond Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tautomer Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">44</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Exact Mass</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">282.07712</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MonoIsotopic Mass</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">282.07712</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Topological Polar Surface Area</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">75.4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Heavy Atom Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">19</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Formal Charge</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Complexity</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">298</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Isotope Atom Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Defined Atom StereoCenter Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Undefined Atom StereoCenter Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Defined Bond StereoCenter Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Undefined Bond StereoCenter Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Covalently-Bonded Unit Count</td><td rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">2</td></tr></tbody></table></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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