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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease - Chemotype 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="Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease - Chemotype 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="2011/03/25">
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<meta name="citation_author" content="Omid Motabar">
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<meta name="citation_author" content="Wenwei Huang">
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<meta name="citation_author" content="Juan Jose Marugan">
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<meta name="citation_author" content="Noel Southall">
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<meta name="citation_author" content="Maria DeBernardi">
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<meta name="citation_author" content="Wei Zheng">
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<meta name="citation_author" content="Ellen Sidransky">
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<meta name="citation_pmid" content="21735598">
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<meta name="DC.Title" content="Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease - Chemotype 2">
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<meta name="DC.Contributor" content="Omid Motabar">
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<meta name="DC.Contributor" content="Wenwei Huang">
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<meta name="DC.Contributor" content="Juan Jose Marugan">
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<meta name="DC.Contributor" content="Noel Southall">
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<meta name="DC.Contributor" content="Maria DeBernardi">
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<meta name="DC.Contributor" content="Wei Zheng">
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<meta name="DC.Contributor" content="Ellen Sidransky">
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<meta name="DC.Date" content="2011/03/25">
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<meta name="description" content="Known glycosidase chaperone molecules belong to the aminosugar class. Because iminosugar inhibitors work by mimicking the transition state of the glycosidic cleavage, they tend to be poorly selective. This has hampered their advance in clinical development. Alternative scaffolds with chaperone activity are quite desirable. Here, we present a new non-aminosugar series of glucocerebrosidase inhibitors having chaperone capacity. The probe, ML156 (CID 9893924), is able to inhibit the hydrolytic activity of the N370S mutant form of glucocerebrosidase. Most importantly, ML156 (CID 9893924) increased glucocerebrosidase translocation to the lysosome in Gaucher patient-derived fibroblasts homozygous for the N370S mutation, and can be used to study ER-lysosomal trafficking of clinically relevant GC mutants in vitro. This probe may be a useful lead for the pre-clinical development of a chemical chaperone of glucocerebrosidase.">
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<meta name="og:description" content="Known glycosidase chaperone molecules belong to the aminosugar class. Because iminosugar inhibitors work by mimicking the transition state of the glycosidic cleavage, they tend to be poorly selective. This has hampered their advance in clinical development. Alternative scaffolds with chaperone activity are quite desirable. Here, we present a new non-aminosugar series of glucocerebrosidase inhibitors having chaperone capacity. The probe, ML156 (CID 9893924), is able to inhibit the hydrolytic activity of the N370S mutant form of glucocerebrosidase. Most importantly, ML156 (CID 9893924) increased glucocerebrosidase translocation to the lysosome in Gaucher patient-derived fibroblasts homozygous for the N370S mutation, and can be used to study ER-lysosomal trafficking of clinically relevant GC mutants in vitro. This probe may be a useful lead for the pre-clinical development of a chemical chaperone of glucocerebrosidase.">
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cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav 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="_NBK56229_"><span class="title" itemprop="name">Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential
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Therapy for Gaucher Disease - Chemotype 2</span></h1><p class="contribs">Motabar O, Huang W, Marugan JJ, et al.</p><p class="fm-aai"><a href="#_NBK56229_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>Known glycosidase chaperone molecules belong to the aminosugar class. Because iminosugar inhibitors work by mimicking the transition state of the glycosidic cleavage, they tend to be poorly selective. This has hampered their advance in clinical development. Alternative scaffolds with chaperone activity are quite desirable. Here, we present a new non-aminosugar series of glucocerebrosidase inhibitors having chaperone capacity. The probe, <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a> (CID 9893924), is able to inhibit the hydrolytic activity of the N370S mutant form of glucocerebrosidase. Most importantly, <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a> (CID 9893924) increased glucocerebrosidase translocation to the lysosome in Gaucher patient-derived fibroblasts homozygous for the N370S mutation, and can be used to study ER-lysosomal trafficking of clinically relevant GC mutants <i>in vitro</i>. This probe may be a useful lead for the pre-clinical development of a chemical chaperone of glucocerebrosidase.</p></div><div class="h2"></div><p><b>Assigned Grant Number:</b> MH086442-01</p><p><b>Screening Center Name & PI:</b> NIH Chemical Genomics Center, Dr. Christopher P. Austin</p><p><b>Chemistry Center Name & PI:</b> NIH Chemical Genomics Center, Dr. Christopher P. Austin</p><p><b>Assay Submitter & Institution:</b> NIH Human Genome Research Institute, Dr. Ellen Sidransky</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2593" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2593</a></p><div id="ml156.s1"><h2 id="_ml156_s1_">Probe Structure & Characteristics</h2><div id="ml156.fu1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu1.jpg" alt="ML156." /></div><h3><span class="title"><a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a></span></h3></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156tu1"><a href="/books/NBK56229/table/ml156.tu1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml156tu1" rid-ob="figobml156tu1"><img class="small-thumb" src="/books/NBK56229/table/ml156.tu1/?report=thumb" src-large="/books/NBK56229/table/ml156.tu1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml156.tu1"><a href="/books/NBK56229/table/ml156.tu1/?report=objectonly" target="object" rid-ob="figobml156tu1">Table</a></h4></div></div></div><div id="ml156.s2"><h2 id="_ml156_s2_">Recommendations for scientific use of the probe</h2><p>Known glycosidase chaperone molecules belong to the aminosugar class. Because iminosugar inhibitors work by mimicking the transition state of the glycosidic cleavage, they tend to be poorly selective. This has hampered their advance in clinical development. Alternative scaffolds with chaperone activity are quite desirable. Here, we present a new non-aminosugar series of glucocerebrosidase inhibitors having chaperone capacity. The probe is able to inhibit the hydrolytic activity of the N370S mutant form of glucocerebrosidase. Most importantly, the probe increased glucocerebrosidase translocation to the lysosome in Gaucher patient-derived fibroblasts homozygous for the N370S mutation, and can be used to study ER-lysosomal trafficking of clinically relevant GC mutants <i>in vitro</i>. This probe may be a useful lead for the pre-clinical development of a chemical chaperone of glucocerebrosidase.</p></div><div id="ml156.s3"><h2 id="_ml156_s3_">1. Introduction</h2><p>Gaucher disease, the most common of the lipidoses, is an autosomal recessive disorder resulting from mutations in the enzyme glucocerebrosidase (EC 3.2.1.45)<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>. The function of glucocerebrosidase (GC) is to hydrolyze beta glycosidic linkages of glucocerebrosides, also called glucosylceramides, in the lysosome<a class="bibr" href="#ml156.r2" rid="ml156.r2">2</a>. These glycosphingolipids are cell membrane components that maintain the stability of the lipid bilayer, function as cellular recognition elements and play an important role in cellular adherence<a class="bibr" href="#ml156.r3" rid="ml156.r3">3</a>.</p><p>There are more than 200 recognized mutations in the glucocerebrosidase gene<a class="bibr" href="#ml156.r4" rid="ml156.r4">4</a>. Although many GC mutants are still functional<a class="bibr" href="#ml156.r5" rid="ml156.r5">5</a>, many affect translocation to the lysosome, which results in protein premature degradation in the ER. The inability of GC protein to reach the lysosome produces accumulation of glucosylceramides in the lysosome, causing tissue-specific lysosomal enlargement, which is characteristic of the disease. Currently, the major FDA approved medication for the treatment of Gaucher disease is the infusion of recombinant human enzyme as enzymatic replacement therapy (ERT). Although ERT successfully reverses some of the disease manifestations, the limited tissue distribution of the infused enzyme to the CNS and lungs and its high cost require the need for improvement<a class="bibr" href="#ml156.r6" rid="ml156.r6">6</a>.</p><p>A proposed alternate therapeutic strategy is the use of small molecular chaperones to restore the cellular function of the mutant enzyme. Small molecules that bind the mutant protein can facilitate its proper folding and increase the translocation of the mutant enzyme to the lysosome<a class="bibr" href="#ml156.r7" rid="ml156.r7 ml156.r8">7–8</a>. Several iminosugar inhibitors of glycosidases have been reported to have chaperone activity<a class="bibr" href="#ml156.r9" rid="ml156.r9 ml156.r10 ml156.r11 ml156.r12 ml156.r13 ml156.r14 ml156.r15 ml156.r16 ml156.r17 ml156.r18 ml156.r19 ml156.r20">9–20</a>. For GC, two iminosugars have been clinical evaluated: Genz-112638<a class="bibr" href="#ml156.r21" rid="ml156.r21">21</a>, currently in clinical trials, and isofagomine (Afegostat<a class="bibr" href="#ml156.r22" rid="ml156.r22">22</a>), whose development was recently halted during phase II testing. Because iminosugar inhibitors work by mimicking the transition state of the glycosidic cleavage, they tend to be poorly selective<a class="bibr" href="#ml156.r13" rid="ml156.r13">13</a>. Alternative scaffolds with chaperone activity are quite desirable. In addition, it is important that the compound inhibitory potency is not the primary determinant of therapeutic potential, because native substrates need to be able to displace the inhibitor after translocation to the lysosome<a class="bibr" href="#ml156.r2" rid="ml156.r2">2</a>, <a class="bibr" href="#ml156.r8" rid="ml156.r8">8</a>, <a class="bibr" href="#ml156.r23" rid="ml156.r23">23</a>. Thus, the molecules that have moved to clinical testing are not the most potent inhibitors known<a class="bibr" href="#ml156.r24" rid="ml156.r24">24</a>.</p><p>A goal of the current study was to develop a non-iminosugar series with a favorable balance between inhibitory potency and chaperone activity. In the cell, GC activity is modulated through the binding of an allosteric activator, Saposin C<a class="bibr" href="#ml156.r25" rid="ml156.r25">25</a>. In isolation, the addition of a bile salt is required to induce GC activity<a class="bibr" href="#ml156.r26" rid="ml156.r26">26</a>. A series of GC inhibitors identified by screening with purified enzyme were found to have reduced or absent activity when tested in tissue homogenate assays. We speculate that this difference in activity is due to nonspecific protein binding and/or to GC conformational differences between the conformation induced by detergent and that induced by Saposin C. In addition, activity differences are observed between wildtype and mutant enzyme.</p><p>As 70 % of Gaucher patients carry the N370S mutation, we focused our efforts on the use of spleen<a class="bibr" href="#ml156.r27" rid="ml156.r27">27</a> homogenate homozygous for the N370S mutation for screening for GC inhibitors and activators. GC specific activity was evaluated using 4-methylumbelliferone β–D-glucopyranoside. Upon hydrolysis, the blue dye 4-methylumbelliferone (4-MU) was liberated, producing a fluorescent emission at 440 nm when excited at 370 nm. Active compounds were then further characterized in several additional assays to confirm specificity, rule out artifacts, and most importantly, characterize chaperone activity.</p></div><div id="ml156.s4"><h2 id="_ml156_s4_">2. Materials and Methods</h2><div id="ml156.s5"><h3>Chemistry</h3><p>All commercially available reagents and solvents were purchased and used without further purification. All microwave reactions were carried out in a sealed microwave vial equipped with a magnetic stir bar and heated in a Biotage Initiator Microwave Synthesizer. HPLC purification was performed using a Waters semi-preparative HPLC equipped with a Phenomenex Luna<sup>®</sup> C18 reverse phase (5 micron, 30× 75mm) column having a flow rate of 45 ml/min. The mobile phase was a mixture of acetonitrile and H<sub>2</sub>O, each containing 0.1% trifluoroacetic acid. During purification, a gradient of 30% to 80% acetonitrile over 8 minutes was used with fraction collection triggered by UV detection (220nM). <sup>1</sup>H spectra were recorded using either an Inova 400 MHz spectrometer (Varian) or an Inova 300 MHz spectrometer (Varian). Two LCMS methods were used to analyze samples’ purity.</p><p>Method 1: Agilent 1200 series LC/MS equipped with a Zorbax™ Eclipse XDB-C18 reverse phase (5 micron, 4.6× 150mm) column having a flow rate of 1.1 ml/min. The mobile phase was a mixture of acetonitrile and H<sub>2</sub>O, each containing 0.05% trifluoroacetic acid. A gradient of 5% to 100% acetonitrile over 8 minutes was used during analytical analysis.</p><p>Method 2: Acquity HPLC equipped with a Waters BEH C18, 1.7 micron, 2.1 × 50 mm column; Column Temperature: 45 degrees C; Flow: 0.5ml/min; Solvent A: 0.05% TFA in Water; Solvent B: 0.025% TFA in Acetonitrile; Gradient: 2% to 100% Solvent B over 1.3 minutes; Run Time - 3 min.</p></div><div id="ml156.s6"><h3>Biology</h3><p>The recombinant wildtype enzyme, Cerezyme®, was obtained from Genzyme Corporation (Cambridge, MA). N370S recombinant glucocerebrosidase was a gift from Dr. Tim Edmunds at Genzyme. Patients’ spleens were obtained from splenectomies with informed consent under an NIH-IRB approved clinical protocol. Control spleens were obtained under an NIH protocol. 4-methylumbelliferyl-β-D-glucopyranoside (4MU-β-glc), a blue fluorogenic substrate, resorufin β-D-glucopyranoside (res-β-glc), a red fluorogenic substrate, sodium taurocholate, and the buffer components were purchased from Sigma-Aldrich (St. Louis, MO). Isofagomine and N-nonyl-deoxynojirimycin (NN-DNJ) were purchased from Toronto Research Biochemicals (Ontario, Canada).</p></div><div id="ml156.s7"><h3>2.1. Assays</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t1"><a href="/books/NBK56229/table/ml156.t1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figml156t1" rid-ob="figobml156t1"><img class="small-thumb" src="/books/NBK56229/table/ml156.t1/?report=thumb" src-large="/books/NBK56229/table/ml156.t1/?report=previmg" alt="Table 1. Assay protocols and data deposited into PubChem." /></a><div class="icnblk_cntnt"><h4 id="ml156.t1"><a href="/books/NBK56229/table/ml156.t1/?report=objectonly" target="object" rid-ob="figobml156t1">Table 1</a></h4><p class="float-caption no_bottom_margin">Assay protocols and data deposited into PubChem. </p></div></div><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2101</a>:</b> qHTS assay for activators and inhibitors of N370S Mutant Form of Glucocerebrosidase</p><p>This is a fluorogenic enzyme assay with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate and the glucocerebrosidase from spleen homogenate of a N370S Gaucher patient as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation.</p><p>The human spleen tissue was homogenized using a food blender at the maximal speed for 5 minutes, followed by 10 passes in a motor-driven 50ml glass-Teflon homogenizer. The homogenate was centrifuged at 1000 ×g for 10 min. The supernatant was then filtered using a 40μm filter and aliquots of resultant spleen homogenate were frozen at −80°C until use. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of spleen homogenate (27μg final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37° C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10)</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2590</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Primary Screen Confirmation</p><p>This is a fluorogenic enzyme assay with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate and N370S glucocerebrosidase from human spleen homogenate as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of spleen homogenate (27μg final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37°C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2613" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2613</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Activity in N370S Spleen Homogenate Using a Red Fluorescent Substrate</p><p>This is a fluorogenic enzyme assay with resorufin-beta-D-glucopyranoside as the substrate and mutant N370S glucocerebrosidase from human spleen homogenate as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of spleen homogenate (27μg final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2592" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2592</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Activity in Non-Mutant Spleen Homogenate</p><p>This is a fluorogenic enzyme assay with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate and wildtype glucocerebrosidase from human spleen homogenate as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of spleen homogenate (27μg final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2588" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2588</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Activity in Non-Mutant Spleen Homogenate Using a Red Fluorescent Substrate</p><p>This is a fluorogenic enzyme assay with resorufin-beta-D-glucopyranoside as the substrate and wildtype glucocerebrosidase from human spleen homogenate as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of spleen homogenate (27μg final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2595" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2595</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Purified Non-mutant Glucocerebrosidase</p><p>This assay characterizes compound activity using purified wildtype enzyme instead of mutant enzyme from tissue homogenate. Compound activity differences may be due to the absence of endogenous cofactors found in tissue homogenate, as well as inherent differences in enzyme stability and catalytic activity between the N370S and wildtype forms of the protein. This is a fluorogenic enzyme assay, with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate and purified wildtype glucocerebrosidase as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of glucocerebrosidase enzyme solution (5nM final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2597" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2597</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Purified N370S Glucocerebrosidase</p><p>This assay characterizes compound activity using purified mutant enzyme instead of tissue homogenate. Compound activity differences may be due to the absence of endogenous cofactors found in tissue homogenate. This is a fluorogenic enzyme assay, with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate and purified N370S glucocerebrosidase as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 4-methyllumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 100mM potassium chloride, 10mM sodium chloride, 1mM magnesium chloride, 0.01% Tween-20.)</p><p>1536-well assay protocol:</p><ol><li class="half_rhythm"><div>Add 2 μl/well of glucocerebrosidase enzyme solution (5nM final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.5nM to 58μM.</div></li><li class="half_rhythm"><div>Add 2μl of substrate (1mM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2596" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2596</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Purified N370S Glucocerebrosidase Cleavage of Glucosylceramide</p><p>This assay characterizes compound activity using purified, mutant enzyme cleavage of the native substrate for the enzyme instead of mutant enzyme from tissue homogenate. Compound activity differences may be due to the absence of endogenous cofactors found in tissue homogenate, as well as inherent differences in enzyme stability and catalytic activity using the difference substrates.</p><p>This is an enzyme assay using glucosylceramide from soy (Avanti Polar Lipids Catalog #: 131304P) as the substrate and recombinant human glucocerebrosidase as the enzyme preparation. Upon hydrolysis of the substrate, the glucose product can be detected using the Amplex Red Glucose Oxidase Assay Kit (Invitrogen catalog #: A22189). The product of this reaction can be read with a fluorescence plate reader with an excitation at 573 nm and an emission at 610 nm. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer for enzyme reaction: 50mM citric acid (titrated with potassium phosphate to pH 5.9), 0.01% Tween-20 (pH 5.9 is an optimal condition for this enzyme assay) and assay buffer for Amplex Red reaction: Tris-HCl, pH 7.5.)</p><p>1536-well assay protocol for the glucocerebrosidase assay:</p><ol><li class="half_rhythm"><div>Add 2 μl/well glucocerebrosidase enzyme solution (5nM final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.7nM to 77μM.</div></li><li class="half_rhythm"><div>Add 1μl of glucosylceramide solution (50μM final).</div></li><li class="half_rhythm"><div>Incubate at 37C for 40 min.</div></li><li class="half_rhythm"><div>Add 2 μl Tris-HCl buffer with Amplex Red reagents.</div></li><li class="half_rhythm"><div>Incubate 45 min at room temperature.</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=573 nm and Em=610nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2577</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Alpha-Glucosidase Counterscreen</p><p>To characterize compound selectivity, selected hits from the primary screen were screened against purified alpha-glucosidase, a related sugar hydrolase. Alpha-glucosidase is responsible for hydrolysis of terminal, non-reducing 1,4-linked alpha-D-glucose residues with release of alpha-D-glucose. This is a fluorogenic enzyme assay with 4-methylumbelliferyl-alpha-D-pyranoside as the substrate and human alpha-glucosidase as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 1,4-methylumbelliferone, can be excited at 365 nm and emits at 440 nm; this can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). The AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 5.0), 0.005% Tween-20, pH 5.0 (pH 5.0 is an optimal condition for this enzyme assay).)</p><p>1536-well assay protocol for the human alpha-glucosidase:</p><ol><li class="half_rhythm"><div>Add 2μl/well of enzyme (4nM final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.7nM to 77μM.</div></li><li class="half_rhythm"><div>Add 1μl of substrate (400μM final).</div></li><li class="half_rhythm"><div>Incubate at room temperature for 20 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2578</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Alpha-Galactosidase Counterscreen</p><p>To characterize compound selectivity, selected hits from the primary screen were screened against purified alpha-galactosidase, a related sugar hydrolase. Alpha-galactosidase is a homodimeric glycoprotein that hydrolyzes the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This is a fluorogenic enzyme assay with 4-Methylumbelliferyl alpha-D-galactopyranoside as the substrate and human alpha-galactolucosidase as the enzyme preparation. Upon the hydrolysis of this fluorogenic substrate, the resulting product, 1,4-Methylumbelliferone, can be excited at 365 nm and emits at 440 nm. This fluorescence can be detected by a standard fluorescence plate reader. Data were normalized to the controls for basal activity (without enzyme) and 100% activity (with enzyme). AC<sub>50</sub> values were determined from concentration-response data modeled with the standard Hill equation. (Assay buffer: 50mM citric acid (titrated with potassium phosphate to pH 4.5), 0.005% Tween-20, pH 4.5 (pH 4.5 is an optimal condition for this enzyme assay).)</p><p>1536-well assay protocol for the human alpha-galactosidase:</p><ol><li class="half_rhythm"><div>Add 2μl/well of enzyme (12nM final).</div></li><li class="half_rhythm"><div>Add 23nl compounds in DMSO solution. The final titration was 0.7nM to 77μM.</div></li><li class="half_rhythm"><div>Add 1μl of substrate (80μM final).</div></li><li class="half_rhythm"><div>Incubate at room temperature for 20 min.</div></li><li class="half_rhythm"><div>Add 2μl stop solution (1M NaOH and 1M Glycine mixture, pH 10).</div></li><li class="half_rhythm"><div>Detect the assay plate in a ViewLux plate reader (PerkinElmer) with Ex=365 nm and Em=440nm.</div></li></ol><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2587" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2587</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Chaperone Activity in Gauche Fibroblasts after Multi-day Incubation with Compound</p><p>This assay attempts to quantitate translocated glucocerebrosidase protein in patient-derived fibroblasts following extended compound incubation. The fibroblasts tested in this experiment were homozygous for N370S glucocerebrosidase.</p><p>Primary dermal fibroblasts derived from skin biopsies from two previously described N370S/N370S Gaucher patients (Goker-Alpan <i>et al</i>, 2008)<a class="bibr" href="#ml156.r28" rid="ml156.r28">28</a> and a control were seeded in Lab-Tek 4 chamber slides (Fisher Scientific, Pittsburgh, PA). After compound treatment, fibroblasts were fixed in 3% paraformaldehyde. The cells were permeabilized with 0.1 % Triton-X for 10 min. and blocked in PBS containing 0.1% saponin, 100μM glycine, 0.1% BSA and 2% donkey serum, followed by incubation with mouse monoclonal anti-LAMP1 or LAMP-2 (1:100, Developmental Studies Hybridoma bank, University of Iowa, Iowa City, IA) and the rabbit polyclonal anti-GCase R386 antibody (1:500); the cells were washed and incubated with secondary donkey anti-mouse or anti-rabbit antibodies conjugated to ALEXA-488 or ALEXA-555, respectively (Invitrogen, Carlsbad, CA), washed again, and mounted in VectaShield with DAPI (Vector Laboratories, Burlingame, CA).</p><p>Cells were imaged with a Zeiss 510 META confocal laser-scanning microscope (Carl Zeiss, Microimaging Inc., Germany) using an Argon (458, 477, 488, 514 nm) 30 mW laser, a HeNe (543 nm) 1 mW laser, and a laser diode (405 nm). Low and high magnification images were acquired using a Plan-Apochromat 20X/0.75 objective and a Plan-Apochromat 100x/1.4 oil DIC objective, respectively. Images were taken with the same laser settings, and all images shown are collapsed z-stacks.</p><p><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2589" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2589</a>:</b> qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Chaperone Activity in Non-Gauche Fibroblasts after Multi-day Incubation with Compound</p><p>This assay attempts to quantitate translocated glucocerebrosidase protein in patient-derived fibroblasts following extended compound incubation. The fibroblasts tested in this experiment contain wildtype glucocerebrosidase.</p><p>Protocol Summary:</p><ol><li class="half_rhythm"><div>Seeded 3000 cells/well in 96-well plates using DMEM (10% FBS), with only medium in outer wells to eliminate the edge effect.</div></li><li class="half_rhythm"><div>Next day, replaced medium with OptiMem (2% FBS) and spiked in various concentrations of compound.</div></li><li class="half_rhythm"><div>2 days later, replaced with fresh OptiMem, and again spiked each well the same as before.</div></li><li class="half_rhythm"><div>3 days later, washed 1x with PBS.</div></li><li class="half_rhythm"><div>Incubated with 3% Paraformaldehyde for 15 min, replaced with PBS.</div></li><li class="half_rhythm"><div>Aspirated PBS and added block solution (5% goat serum + 0.1% saposin + 15 mg/ml glycine in PBS) and incubated at RT for 40 min.</div></li><li class="half_rhythm"><div>Aspirated block solution and added r386 antibody solution to stain glucocerebrosidase (20μl Ab in 19ml of 5% goat serum, 0.1% saposin in PBS) (~1:1000 dilution).</div></li><li class="half_rhythm"><div>Left at 4C overnight.</div></li><li class="half_rhythm"><div>Next day, washed 3x with block solution (no glycine). Waited 10 min between washes.</div></li><li class="half_rhythm"><div>Added mix of secondary antibody solution (1:100 dilution of Cy-3 for GC, 1:100 dilution of FITC for LAMP2, 1:5000 dilution of Hoechst) in 5% goat serum solution and incubated 1 hr.</div></li><li class="half_rhythm"><div>Rinsed 3X with PBS, waiting 5 minutes between washes.</div></li><li class="half_rhythm"><div>Visualized using a fluorescence microscope and the intensity of fluorescence in the selected areas were calculated.</div></li></ol><div id="ml156.s8"><h4>LC-MS hydrolysis experiment</h4><p>This assay uses liquid chromatography linked to a mass spectrometer to assess the ability of glucocerebrosidase in the spleen homogenate to cleave its natural substrate (glucosylceramide). The substrate has a fluorescent tag, which allows the cleavage to be measured; however, it is not believed to have a role in the enzymatic reaction. This assay most closely reflects the physiological condition in the body.</p><p>Chromatography was performed using an Agilent HPLC. The Agilent 1200 LC was equipped with a quaternary pump, a G1315 diode array detector, and a G1321 Fluorescent Detector. A 4.6× 250 mm Agilent Eclipse Plus C18 (5 micron) at ambient temperature was used at a flow rate of 1.8 ml/min with a gradient of 85/15 (methanol/0.1% formic acid in water) to 100 methanol over 10 minutes. Compounds were monitored using fluorescence detection with an excitation wavelength of 505 nanometers and emission wavelength at 540 nanometers.</p></div><div id="ml156.s9"><h4>Caco-2 Permeability and Microsomal Stability</h4><p>Analytical signal was optimized for each compound by ESI positive or negative ionization mode. A MS2 SIM scan was used to optimize the precursor ion, and a product ion analysis was used to identify the best fragment for analysis and to optimize the collision energy. Samples were analyzed by LC/MS/MS using either an Agilent 6410 mass spectrometer coupled with an Agilent 1200 HPLC and a CTC PAL chilled autosampler, all controlled by MassHunter software (Agilent), or an ABI2000 mass spectrometer coupled with an Agilent 1100 HPLC and a CTC PAL chilled autosampler, all controlled by Analyst software (ABI). After separation on a C18 reverse phase HPLC column (Agilent, Waters, or equivalent) using an acetonitrile-water gradient system, peaks were analyzed by mass spectrometry (MS) using ESI ionization in MRM mode.</p><p>CaCo-2 cells grown in tissue culture flasks are trypsinized, suspended in medium, and the suspensions were applied to wells of a collagen-coated BioCoat Cell Environment in 24-well format (BD Biosciences) at 24,500 cells per well. The cells are allowed to grow and differentiate for three weeks, feeding at 2-day intervals.</p><p>For Apical to Basolateral (A->B) permeability, the test agent is added to the apical (A) side and amount of permeation is determined on the basolateral (B) side; for Basolateral to Apical (B>A) permeability, the test agent is added to the B side and the amount of permeation is determined on the A side. The A-side buffer contains 100μM Lucifer yellow dye, in Transport Buffer (1.98 g/l glucose in 10mM HEPES, 1x Hank’s Balanced Salt Solution) pH 6.5, and the B-side buffer is Transport Buffer, pH 7.4. CaCo-2 cells are incubated with these buffers for 2 h., and the receiver side buffer is removed for analysis by LC/MS/MS. To verify that CaCo-2 cell monolayers are properly formed, aliquots of the cell buffers are analyzed by fluorescence to determine the transport of the impermeable dye Lucifer Yellow.</p><p>Data are expressed as permeability (Papp):
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<math id="ml156.mu1"><semantics><mrow><msub><mrow><mi>P</mi></mrow><mrow><mi>a</mi><mi>p</mi><mi>p</mi></mrow></msub><mo>=</mo><mfrac><mrow><mi>d</mi><mi>Q</mi><mo>/</mo><mi>d</mi><mi>t</mi></mrow><mrow><msub><mrow><mi>C</mi></mrow><mn>0</mn></msub><mi>A</mi></mrow></mfrac></mrow></semantics></math></span></p><p>where dQ/dt is the rate of permeation, C0 is the initial concentration of test agent, and A is the area of the monolayer. In bidirectional permeability studies, the asymmetry index (AI) or efflux ratio is also calculated:</p><div class="pmc_disp_formula whole_rhythm clearfix" id="ml156.eq1"><div class="inline_block pmc_inline_block pmc_va_middle pmc_hide_overflow twelve_col">
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<math id="ml156.m1" display="block"><semantics><mrow><mtext>AI</mtext><mo>=</mo><mfrac><mrow><msub><mrow><mi>P</mi></mrow><mrow><mi>a</mi><mi>p</mi><mi>p</mi></mrow></msub><mo stretchy="false">(</mo><mi>B</mi><mo>→</mo><mi>A</mi><mo stretchy="false">)</mo></mrow><mrow><msub><mrow><mi>P</mi></mrow><mrow><mi>a</mi><mi>p</mi><mi>p</mi></mrow></msub><mo stretchy="false">(</mo><mi>A</mi><mo>→</mo><mi>B</mi><mo stretchy="false">)</mo></mrow></mfrac></mrow></semantics></math></div><div class="inline_block pmc_inline_block pmc_va_middle pmc_hide_overflow last bk_equ_label "><div><span class="nowrap"></span></div></div></div><p>An AI > 1 indicates a potential substrate for PGP or other active transport.</p><p>For microsomal stability testing, the test agent is incubated in duplicate with microsomes at 37°C. The reaction contains microsomal protein in 100 mM potassium phosphate, 2mM NADPH, 3mM MgCl<sub>2</sub>, pH 7.4. A control is run for each test agent omitting NADPH to detect NADPH-free degradation. At indicated times, an aliquot is removed from each experimental and control reaction and mixed with an equal volume of ice-cold Stop Solution (0.3% acetic acid in acetonitrile containing haloperidol, diclofenac, or other internal standard). Stopped reactions are incubated at least ten minutes at −20°C, and an additional volume of water is added. The samples are centrifuged to remove precipitated protein, and the supernatants are analyzed by LC/MS/MS to quantitate the remaining parent. Data are reported as % remaining by dividing by the time zero concentration value.</p></div><div id="ml156.s10"><h4>Pharmacokinetic Study in Male Swiss Albino Mice</h4><p>Compound was dosed IP at 20 mg/kg to mice and plasma, brain, liver and tail. Concentrations were determined pre-dose and at 0, 5, 15, 30, 60, 120, 240, 480, 720, 780, 900, 1020, and 1440 minutes, with 3 animals per time point. Male Swiss Albino mice used in this experiment were procured from National Institute of Nutrition (NIN), Hyderabad, India. Animals were acclimatized for three days in an animal holding room. Test article CID was dissolved in DMA, TEG and Water for Injection in the ratio of 20:40:40, and vortexed. After dosing of each animal, animals were observed for any abnormal behavioral signs exhibited after drug administration.</p><p>Each mouse was anesthetized using Isoflurane. Blood was collected through a capillary, guided in retro-orbital plexus. The blood samples were collected in prelabeled Heparin coated tubes (BD, cat. No.365965). 0.3ml of blood was collected from each mouse at their respective timepoints. After collection of blood samples at each time point, the blood samples were stored on wet ice prior to centrifugation. Blood samples were centrifuged within 15 minutes to separate plasma at 5000 rpm, 4°C for 10 minutes. The plasma was separated and transferred to pre labeled tubes and promptly frozen at −80 ± 10 °C until bioanalysis. Immediately after blood withdrawal for PK estimation, <i>in situ</i> whole body perfusion was performed using chilled saline. The chest and abdomen of the mouse was exposed, the inferior venacava was cut and Intra-cardiac perfusion was performed through an insertion in the left ventricle. Perfusion for each mouse was followed by decapitation for brain collection. The skin over the cranium was incised and deflected. The head was flexed and a cut was made through the muscles and the spinal cord at the junction of the foramen magnum and atlas vertebra. A circumferential incision was carefully made in the cranium using a pair of small scissors. The roof of the cranium was lifted off to expose the meninges and brain. The meninges were removed carefully. Then holding the head with the nose pointing upward, the anterior part of the brain was lifted to separate the brain. Separated brain was immediately weighed and frozen at −80 ± 10°C until homogenization. PK parameters are calculated for mean concentration by the non-compartmental model, trapezoid rule (linear interpolation method) using WinNonlin Software Version 4.1.</p></div></div><div id="ml156.s11"><h3>2.2. Probe Chemical Characterization</h3><p>Structural verification information of probe <a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449177" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID: 89449177</a>/<a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a></p><p><sup>1</sup>H NMR (400 MHz, CHLOROFORM-<i>d</i>) δ ppm 1.85 – 1.99 (m, 4 H), 2.68 (m, 2 H), 3.61 (m, 6 H), 4.60 (s, 2 H), 6.31 (d, <i>J</i>=9.19 Hz, 1 H), 6.81 (s, 1 H), 7.00 (dd, <i>J</i>=8.31, 1.86 Hz, 1 H), 7.23 (d, <i>J</i>=1.76 Hz, 1 H), 7.36 (d, <i>J</i>=8.22 Hz, 1 H), 7.44 (dd, <i>J</i>=9.00, 2.54 Hz, 1 H), 7.52 (s, 1 H), 8.12 (br. s., 1 H); HRMS (ESI): <i>m/z</i> calcd for C<sub>22</sub>H<sub>25</sub>BrCl<sub>2</sub>N<sub>6</sub>S 554.0422, found 554.0434; LC/MS (Agilent system) Retention time t<sub>1</sub> (short) = 3.33 min and t<sub>2</sub> (long) = 5.25 min; Purity: UV<sub>220</sub> > 99%, UV<sub>254</sub> > 99%; MS m/z 555.1 (M+H); Column: 3× 75 mm Luna C18, 3 micron Run time: 4.5 min (short); 8.5 min (long) Gradient: 4 % to 100 % Mobile phase: Acetonitrile (0.025 % TFA), water (0.05 % TFA). Flow rate: 0.8 to 1.0ml Temperature: 50 °C UV wavelength: 220nm, 254nm.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t2"><a href="/books/NBK56229/table/ml156.t2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figml156t2" rid-ob="figobml156t2"><img class="small-thumb" src="/books/NBK56229/table/ml156.t2/?report=thumb" src-large="/books/NBK56229/table/ml156.t2/?report=previmg" alt="Table 2. Compounds submitted to the MLSMR." /></a><div class="icnblk_cntnt"><h4 id="ml156.t2"><a href="/books/NBK56229/table/ml156.t2/?report=objectonly" target="object" rid-ob="figobml156t2">Table 2</a></h4><p class="float-caption no_bottom_margin">Compounds submitted to the MLSMR. </p></div></div></div><div id="ml156.s12"><h3>2.3. Probe Preparation</h3><div id="ml156.s13"><h4>Synthesis of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a> and analogs</h4><p>NCGC00159568 (<b>8i</b>) and analogs were synthesized as shown in <a class="figpopup" href="/books/NBK56229/figure/ml156.f4/?report=objectonly" target="object" rid-figpopup="figml156f4" rid-ob="figobml156f4">Schemes 1</a>–<a class="figpopup" href="/books/NBK56229/figure/ml156.f6/?report=objectonly" target="object" rid-figpopup="figml156f6" rid-ob="figobml156f6">3</a>. <a class="figpopup" href="/books/NBK56229/figure/ml156.f4/?report=objectonly" target="object" rid-figpopup="figml156f4" rid-ob="figobml156f4">Scheme 1</a> depicts the synthesis of compounds <b>8a-l.</b> Reaction of 2-bromopyridines <b>1a-c</b> with an excess of a diaminoalkane gave pyridines <b>3a-e</b>. The primary amino group of <b>3a-e</b> was protected by a trityl group, giving <b>4a-e</b>. Subsequent alkylation of <b>4a-e</b> with appropriate alkyl halides in DMF using LiHMDS as a base afforded <b>5a-f</b> and <b>5h-I</b>, which were converted to amine <b>6a-i</b> by TFA-mediated trityl group de-protection. The desired ureas <b>8k-l</b> and thioureas <b>8a-j</b> were formed by a one-pot reaction of <b>6</b>, <b>7</b>, and 1,1-thiocarbonyldiimidazole (or 1,1′-carbonyldiimidazole), followed by removal of the trityl protecting group.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml156f4" co-legend-rid="figlgndml156f4"><a href="/books/NBK56229/figure/ml156.f4/?report=objectonly" target="object" title="Scheme 1" class="img_link icnblk_img figpopup" rid-figpopup="figml156f4" rid-ob="figobml156f4"><img class="small-thumb" src="/books/NBK56229/bin/ml156f4.gif" src-large="/books/NBK56229/bin/ml156f4.jpg" alt="Scheme 1. Synthesis of compounds 8a-l." /></a><div class="icnblk_cntnt" id="figlgndml156f4"><h4 id="ml156.f4"><a href="/books/NBK56229/figure/ml156.f4/?report=objectonly" target="object" rid-ob="figobml156f4">Scheme 1</a></h4><p class="float-caption no_bottom_margin">Synthesis of compounds 8a-l. Reagents and conditions: (i) H<sub>2</sub>N(CH<sub>2</sub>)<sub>n</sub>NH<sub>2</sub> (<i>2</i>), pyridine, refluxed; (ii) TrCl, THF, Et<sub>3</sub>N, 0 °C-r.t.; (iii) THF, LiHMDS, R<sub>1</sub>X, r.t.; (iv) TFA, DCM; (v) <i>i</i>PrNEt<sub>2</sub>, <i>7</i>, 1,1′-thiocarbonyldiimidazole (or 1,1′-carbonyldiimidazole), <a href="/books/NBK56229/figure/ml156.f4/?report=objectonly" target="object" rid-ob="figobml156f4">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml156f5" co-legend-rid="figlgndml156f5"><a href="/books/NBK56229/figure/ml156.f5/?report=objectonly" target="object" title="Scheme 2" class="img_link icnblk_img figpopup" rid-figpopup="figml156f5" rid-ob="figobml156f5"><img class="small-thumb" src="/books/NBK56229/bin/ml156f5.gif" src-large="/books/NBK56229/bin/ml156f5.jpg" alt="Scheme 2. Synthesis of compound 10." /></a><div class="icnblk_cntnt" id="figlgndml156f5"><h4 id="ml156.f5"><a href="/books/NBK56229/figure/ml156.f5/?report=objectonly" target="object" rid-ob="figobml156f5">Scheme 2</a></h4><p class="float-caption no_bottom_margin">Synthesis of compound 10. Reagents and conditions: (i) PhB(OH)<sub>2</sub>, Na<sub>2</sub>CO<sub>3</sub>, Pd(PPh<sub>3</sub>)<sub>4</sub>, 100 °C, 2 h; (ii) TFA, DMC; (iii) <i>i</i>PrNEt<sub>2</sub>, <i>7a</i>, 1,1′-thiocarbonyldimididazole, DCM, MW 150 °C, 10 min; (iv) TFA </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml156f6" co-legend-rid="figlgndml156f6"><a href="/books/NBK56229/figure/ml156.f6/?report=objectonly" target="object" title="Scheme 3" class="img_link icnblk_img figpopup" rid-figpopup="figml156f6" rid-ob="figobml156f6"><img class="small-thumb" src="/books/NBK56229/bin/ml156f6.gif" src-large="/books/NBK56229/bin/ml156f6.jpg" alt="Scheme 3. Syntheses of compounds 13a-b." /></a><div class="icnblk_cntnt" id="figlgndml156f6"><h4 id="ml156.f6"><a href="/books/NBK56229/figure/ml156.f6/?report=objectonly" target="object" rid-ob="figobml156f6">Scheme 3</a></h4><p class="float-caption no_bottom_margin">Syntheses of compounds 13a-b. Reagents and conditions: (i) <i>i</i>PrNEt<sub>2</sub>, <i>11</i>, 1,1′-thiocarbonyldimididazole, DCM, MW 130 °C, 10 min; (ii) TFA; (iii) for <i>13b</i> CH<sub>3</sub>COCl </p></div></div><p>Suzuki reaction of <b>5a</b> with phenyl boronic acid followed by trityl group de-protection gave amine <b>9</b>. Thiourea <b>10</b> was formed by a one-pot reaction of <b>9</b>, <b>7a</b>, and 1,1-thiocarbonyldiimidazole, followed by removal of the trityl protecting group (<a class="figpopup" href="/books/NBK56229/figure/ml156.f5/?report=objectonly" target="object" rid-figpopup="figml156f5" rid-ob="figobml156f5">Scheme 2</a>).</p><p>Thiourea <b>12</b> was formed by a one-pot reaction of <b>6a</b>, <b>11</b>, and 1,1-thiocarbonyldiimidazole. TFA mediated Boc-deprotection of <b>12</b> afforded <b>13a</b>. Compound <b>13b</b> was formed by reaction of <b>13a</b> with acetic chloride (<a class="figpopup" href="/books/NBK56229/figure/ml156.f6/?report=objectonly" target="object" rid-figpopup="figml156f6" rid-ob="figobml156f6">Scheme 3</a>).</p></div><div id="ml156.s14"><h4>Example: Synthesis of 1-[3-[(5-bromopyridin-2-yl)-[(3,4-dichlorophenyl)methyl]amino]propyl]-3-[3-(1H-imidazol-5-yl)propyl]thiourea (8i)</h4><div id="ml156.fu2" class="figure"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu2.jpg" alt="Image ml156fu2" /></div></div></div><div id="ml156.s15"><h4>N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)propane-1,3-diamine (3a)</h4><div id="ml156.fu3" class="figure"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu3.jpg" alt="Image ml156fu3" /></div></div><p>A mixture of 2, 5-dibromopyridine (<b>1a</b>, 2.0g, 8.4mmol), pyridine (0.8g, 10.1mmol), and 1, 3-diaminopropane (10 mL) was refluxed for 18 hours. The reaction mixture was evaporated <i>in vacuo</i> and 15 mL of anhydrous dichloromethane was added. After filtering off white precipitate, the filtrate was concentrated to yield N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)propane-1,3-diamine <b>(3a,</b> 1.6g, 83%) as an oil.</p></div><div id="ml156.s16"><h4>N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<sup>3</sup>-tritylpropane-1,3-diamine (4a)</h4><div id="ml156.fu4" class="figure"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu4.jpg" alt="Image ml156fu4" /></div></div><p>Trityl chloride (7.3g, 26mmol) was added slowly at 0°C to a mixture of N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)propane-1,3-diamine (<b>3a</b>, 5.0g, 21.7mmol) and triethylamine (2.6g, 26mmol) in anhydrous dichloromethane (50ml). After stirring at room temperature for 1 hour, the reaction mixture was washed with water (3× 10ml). The organic layer was dried over Na<sub>2</sub>SO<sub>4</sub>, filtered, and concentrated. The residue was washed with methanol to afford N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<sup>3</sup>-tritylpropane-1,3-diamine (<b>4a</b>, 9.6g, 79%) as a solid.</p></div><div id="ml156.s17"><h4>N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(3,4-dichlorobenzyl)propane-1,3-diamine (6i)</h4><div id="ml156.fu5" class="figure"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu5.jpg" alt="Image ml156fu5" /></div></div><p>LiHMDS (6ml, 1.0M in THF) was added under nitrogen atmosphere at room temperature to a solution of N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<sup>3</sup>-tritylpropane-1,3-diamine <b>(4a,</b> 940mg, 2mmol) in anhydrous tetrahydrofuran (10ml). After stirring for a half hour, 1-(bromomethyl)-3,4-dichlorobenzene (2.37g, 10mmol) in 10ml of anhydrous THF was added slowly at room temperature. The solution was stirred at room temperature for another hour after addition. The reaction mixture was then poured into ice water (100ml) and extracted with ethyl acetate (3× 30ml). The combined organic layers were washed with water (20ml), dried over Na<sub>2</sub>SO<sub>4</sub>, filtered, and concentrated. The crude product was purified by silica column chromatography using hexanes/ethyl acetate (80:1) to yield <b>5i</b> (0.72g, 57%). N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(3,4-dichlorobenzyl)-N<sup>3</sup>-tritylpropane-1,3-diamine (<b>5i,</b> 629mg, 1.0mmol) was dissolved in DCM/TFA (5ml/5ml). The mixture was stirred at room temperature for 1 hour. Volatile was removed under vacuum and the residue was dissolved in methanol (50ml). The methanol solution was washed by hexanes (10× 10ml) and neutralized to pH=7–8 using 1M NaOH aqueous solution. Then the mixture was extracted with DCM (3× 10ml). The combined organic extracts were dried over Na<sub>2</sub>SO<sub>4</sub>, filtered, and concentrated to yield N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(5-bromopyridin-2-yl)-N<a class="bibr" href="#ml156.r1" rid="ml156.r1">1</a>-(3,4-dichlorobenzyl)propane-1,3-diamine (<b>6i</b>, 310 mg, yield: 80 %). <sup>1</sup>H NMR (300 MHz, CD3OD) δ ppm 8.26 (d, J = 2.4 Hz, 1H), 7.39 (dd, J = 2.4 Hz, 9 Hz, 1H), 7.34 – 7.25 (m, 1H), 7.20 (d, J = 1.5 Hz, 1H), 6.95 (dd, J = 2.1 Hz, 8.4 Hz, 1H), 6.28 (d, J = 9 Hz, 1H), 4.53 (s, 2H), 3.70 (t, J = 7.3 Hz, 2H), 3.04 (t, J = 6.3 Hz, 2H), 2.11 – 2.07 (m, 2H).</p></div><div id="ml156.s18"><h4>1-[3-[(5-bromopyridin-2-yl)-[(3,4-dichlorophenyl)methyl]amino]propyl]-3-[3-(1H-imidazol-5-yl)propyl]thiourea (8i)</h4><div id="ml156.fu6" class="figure"><div class="graphic"><img src="/books/NBK56229/bin/ml156fu6.jpg" alt="Image ml156fu6" /></div></div><p>1,1′-thiocarbonyldimididazole (28.5mg, 0.16mmol, 1equiv) was added to a solution of <b>6i</b> (62.0mg, 0.16mmol, 1equiv) in DCM (1.5ml). The mixture was stirred at room temperature for 3 hours. After that, a solution of <b>7a</b> (58.7mg, 0.16mmol, 1equiv) and DIPEA (10.3mg, 0.08mmol) in CH<sub>3</sub>CN (1.5ml) was added. The mixture was heated at 150°C for 10 minutes under microwave irradiation. After removing solvent, the residue was dissolved in 3ml of DCM. 3ml of TFA at 0°C was added to this solution, and the mixture was stirred at room temperature for 2 hours. Volatile was removed and the residue was purified by HPLC to afford <b>8i</b> (20.4mg, 23%). <sup>1</sup>H NMR (400 MHz, CHLOROFORM-<i>d</i>) δ ppm 1.85 – 1.99 (m, 4 H), 2.68 (m, 2 H), 3.61 (m, 6 H), 4.60 (s, 2 H), 6.31 (d, <i>J</i>=9.19 Hz, 1 H), 6.81 (s, 1 H), 7.00 (dd, <i>J</i>=8.31, 1.86 Hz, 1 H), 7.23 (d, <i>J</i>=1.76 Hz, 1 H), 7.36 (d, <i>J</i>=8.22 Hz, 1 H), 7.44 (dd, <i>J</i>=9.00, 2.54 Hz, 1 H), 7.52 (s, 1 H), 8.12 (br. s., 1 H); HPLC (method 1): t<sub>R</sub> = 5.25 min, UV<sub>220</sub> = 99%; MS m/z 555.1 (M+H); HRMS (ESI): <i>m/z</i> calcd for C<sub>23</sub>H<sub>27</sub>BrClN<sub>5</sub>S HRMS (ESI): <i>m/z</i> calcd for C<sub>22</sub>H<sub>25</sub>BrCl<sub>2</sub>N<sub>6</sub>S 554.0422, found 554.0434.</p></div></div></div><div id="ml156.s19"><h2 id="_ml156_s19_">3. Results</h2><div id="ml156.s20"><h3>3.1. Summary of Screening Results</h3><p>1,300 1536-well plates were screened in qHTS format (most compounds were assayed in titration from 90nM to 57μM final concentration in the primary screen) with a Z′ of 0.80 +/− 0.16 across the entire set of plates, indicating robust performance of the assay. A total of 326,770 compounds were screened<a class="bibr" href="#ml156.r22" rid="ml156.r22 ml156.r23">22–23</a> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2101</a>).</p><p>From the primary screen, we identified several series of modulators, including several imino sugar molecules previously reported to inhibit the enzyme, such as isofagomine.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t3"><a href="/books/NBK56229/table/ml156.t3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml156t3" rid-ob="figobml156t3"><img class="small-thumb" src="/books/NBK56229/table/ml156.t3/?report=thumb" src-large="/books/NBK56229/table/ml156.t3/?report=previmg" alt="Table 3. Compound representatives of initial hit series." /></a><div class="icnblk_cntnt"><h4 id="ml156.t3"><a href="/books/NBK56229/table/ml156.t3/?report=objectonly" target="object" rid-ob="figobml156t3">Table 3</a></h4><p class="float-caption no_bottom_margin">Compound representatives of initial hit series. Isofagomine is an imino sugar previously reported to chaperone glucocerebrosidase. NCGC00092410 is a non-imino sugar previously reported to inhibit purified glucocerebrosidase. </p></div></div></div><div id="ml156.s21"><h3>3.2. Dose Response Curves for Probe</h3><div id="ml156.f1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK56229/bin/ml156f1.jpg" alt="Figure 1. Concentration-response of probe, CID 9893924/ML156, in primary screening assay for N370S GC inhibition from tissue homogenate." /></div><h3><span class="label">Figure 1</span><span class="title">Concentration-response of probe, CID 9893924/<a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>, in primary screening assay for N370S GC inhibition from tissue homogenate</span></h3><div class="caption"><p>Compound IC<sub>50</sub>, measured in triplicate on three different days, was 580 +/− 30nM.</p></div></div></div><div id="ml156.s22"><h3>3.3. Scaffold/Moiety Chemical Liabilities</h3><p>The probe molecule does not contain any functional groups with potential chemical liabilities.</p></div><div id="ml156.s23"><h3>3.4. SAR Tables</h3><p>All analogs were tested in a N370S spleen homogenate assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/AID2590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID2590</a>) to evaluate their inhibitory activity (<a class="figpopup" href="/books/NBK56229/table/ml156.t4/?report=objectonly" target="object" rid-figpopup="figml156t4" rid-ob="figobml156t4">Table 4</a>). The hit compound (<b>8i</b>) was synthesized in house, and the synthesized sample and the purchased sample had the same activity (entries 1–2). Several positions of the hit compound (NCGC00159568, <b>8i</b>) were explored for SAR, and the results are summarized as follows: (a) Decreasing the size of the R1 substituent gradually weakened activity (entries 2–6); (b) At the R2 position, phenyl group at C5 showed better activity than the phenyl group at C4 (entries 8–9); (c) Ureas had similar activities as thiourea (<b>8i</b>
|
|
<i>vs</i>
|
|
<b>8j</b> and <b>8a</b>
|
|
<i>vs</i>
|
|
<b>8k</b>); (d) While decreasing the distance between the thiourea group and the pyridyl moiety from 4C to 2C resulted in a small decrease in activity (entries 9–11), decreasing the distance between the thiourea group and the imidazole group from 3C to 2C resulted in a 30-fold loss of activity (<b>8i</b>
|
|
<i>vs.</i>
|
|
<b>8l</b>); (e) The imidazole group at the R3 position is important for the activity. Replacing the imidazole with an amino group (entry 15), or an acetamide (entry 16), or an methyl group (entry 17) resulted in significant reduction or complete loss of activity; (f) While replacing one of the thiourea NH with a methyl group as in <b>26</b> resulted in loss of 2-fold of activity (entry 20), replacing the other thiourea NH with a methyl group as in <b>27</b> resulted in a 10-fold loss of activity (entry 21); (g) Replacing the pyridine ring with a benzene ring as in <b>24</b> gave similar activity (entry 22).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t4"><a href="/books/NBK56229/table/ml156.t4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml156t4" rid-ob="figobml156t4"><img class="small-thumb" src="/books/NBK56229/table/ml156.t4/?report=thumb" src-large="/books/NBK56229/table/ml156.t4/?report=previmg" alt="Table 4. Structure activity relationship (SAR)." /></a><div class="icnblk_cntnt"><h4 id="ml156.t4"><a href="/books/NBK56229/table/ml156.t4/?report=objectonly" target="object" rid-ob="figobml156t4">Table 4</a></h4><p class="float-caption no_bottom_margin">Structure activity relationship (SAR). </p></div></div><div id="ml156.s24"><h4>Activity of quinazoline analogs</h4><p><a class="figpopup" href="/books/NBK56229/table/ml156.t5/?report=objectonly" target="object" rid-figpopup="figml156t5" rid-ob="figobml156t5">Tables 5</a>–<a class="figpopup" href="/books/NBK56229/table/ml156.t9/?report=objectonly" target="object" rid-figpopup="figml156t9" rid-ob="figobml156t9">9</a> show the capacity of compounds to inhibit the hydrolysis of 4-methylumbelliferone β-D-glucopyranoside. As positive control, we measure the activity of Isofagomine in the same assay (AC50 = 0.080μM).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t5"><a href="/books/NBK56229/table/ml156.t5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figml156t5" rid-ob="figobml156t5"><img class="small-thumb" src="/books/NBK56229/table/ml156.t5/?report=thumb" src-large="/books/NBK56229/table/ml156.t5/?report=previmg" alt="Table 5. Analogs with sulfonamide aromatic modifications having a phenyl at two positions." /></a><div class="icnblk_cntnt"><h4 id="ml156.t5"><a href="/books/NBK56229/table/ml156.t5/?report=objectonly" target="object" rid-ob="figobml156t5">Table 5</a></h4><p class="float-caption no_bottom_margin">Analogs with sulfonamide aromatic modifications having a phenyl at two positions. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t6"><a href="/books/NBK56229/table/ml156.t6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figml156t6" rid-ob="figobml156t6"><img class="small-thumb" src="/books/NBK56229/table/ml156.t6/?report=thumb" src-large="/books/NBK56229/table/ml156.t6/?report=previmg" alt="Table 6. Analogs with sulfonamide aromatic modifications having a thiophene at two positions." /></a><div class="icnblk_cntnt"><h4 id="ml156.t6"><a href="/books/NBK56229/table/ml156.t6/?report=objectonly" target="object" rid-ob="figobml156t6">Table 6</a></h4><p class="float-caption no_bottom_margin">Analogs with sulfonamide aromatic modifications having a thiophene at two positions. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t7"><a href="/books/NBK56229/table/ml156.t7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figml156t7" rid-ob="figobml156t7"><img class="small-thumb" src="/books/NBK56229/table/ml156.t7/?report=thumb" src-large="/books/NBK56229/table/ml156.t7/?report=previmg" alt="Table 7. Analogues with the modifications at the linker." /></a><div class="icnblk_cntnt"><h4 id="ml156.t7"><a href="/books/NBK56229/table/ml156.t7/?report=objectonly" target="object" rid-ob="figobml156t7">Table 7</a></h4><p class="float-caption no_bottom_margin">Analogues with the modifications at the linker. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t8"><a href="/books/NBK56229/table/ml156.t8/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img figpopup" rid-figpopup="figml156t8" rid-ob="figobml156t8"><img class="small-thumb" src="/books/NBK56229/table/ml156.t8/?report=thumb" src-large="/books/NBK56229/table/ml156.t8/?report=previmg" alt="Table 8. Analogs with modification at the 2 position of the quinazoline core." /></a><div class="icnblk_cntnt"><h4 id="ml156.t8"><a href="/books/NBK56229/table/ml156.t8/?report=objectonly" target="object" rid-ob="figobml156t8">Table 8</a></h4><p class="float-caption no_bottom_margin">Analogs with modification at the 2 position of the quinazoline core. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t9"><a href="/books/NBK56229/table/ml156.t9/?report=objectonly" target="object" title="Table 9" class="img_link icnblk_img figpopup" rid-figpopup="figml156t9" rid-ob="figobml156t9"><img class="small-thumb" src="/books/NBK56229/table/ml156.t9/?report=thumb" src-large="/books/NBK56229/table/ml156.t9/?report=previmg" alt="Table 9. Analogs with modifications at the molecular core." /></a><div class="icnblk_cntnt"><h4 id="ml156.t9"><a href="/books/NBK56229/table/ml156.t9/?report=objectonly" target="object" rid-ob="figobml156t9">Table 9</a></h4><p class="float-caption no_bottom_margin">Analogs with modifications at the molecular core. </p></div></div><p>SAR of the series shows very strict requirements for maintaining activity values. <a class="figpopup" href="/books/NBK56229/table/ml156.t5/?report=objectonly" target="object" rid-figpopup="figml156t5" rid-ob="figobml156t5">Tables 5</a> and <a class="figpopup" href="/books/NBK56229/table/ml156.t6/?report=objectonly" target="object" rid-figpopup="figml156t6" rid-ob="figobml156t6">6</a> show the activity of analogs with sulfonamide aromatic modifications. In general, potency changes up to 25-fold between aromatic substituents. Derivatives with a single substitution in the para, and especially in the ortho position, tend to provide better activity. The para methyl analog was one of our most potent compounds with an IC<sub>50</sub> of 320nM. As a group, there are not big differences between the activity provide by halogen, electron-withdrawing and electron-donating functional groups. Bicyclic rings, with combinations of electron-donating groups in meta and para positions (<b>146</b>, <b>147</b> and <b>150</b>) provide the most potent compounds.</p><p>We also studied modifications in the piperidine linker. It can be seen that elimination of the aromatic ring of the sulphonamide is detrimental for the activity of the molecule (<b>172</b>, <b>173</b>, <b>174</b>). In addition, replacement of the sulphone by a carbonyl group also reduces the activity (<b>175</b> and <b>176</b>). This reduction is even greater when the sulphone is eliminated and a benzyl substituent is directly attached to the piperidine ring (<b>177</b>). Analogs <b>178</b> and <b>179</b> show that both nitrogens of the piperidine ring play an important role in maintaining the activity, the one next to the quinazoline ring being the most important. The angle (<b>180</b>) and rigidity (<b>165</b> and <b>166</b>) of the linker is also important for activity.</p><p>The next modifications that we studied were replacement of the aromatic substituent at the two position of the quinazoline ring. <a class="figpopup" href="/books/NBK56229/table/ml156.t8/?report=objectonly" target="object" rid-figpopup="figml156t8" rid-ob="figobml156t8">Table 8</a> shows that complete elimination of the substitution (<b>181</b>) reduces the activity more than 60-fold, and its replacement with non-aromatic functional groups, compounds <b>201</b> to <b>205</b>, have greatly reduced activity. Introduction of an unsubstituted phenyl ring at the 2-position (<b>197</b>) increase the activity of the molecule, although all analogues with substituents in this phenyl ring abolish the activity (<b>198</b>, <b>199</b>, <b>200</b>). Replacement of the phenyl aromatic ring by a six member heteroaromatic ring having one or more nitrogens reduces or abolishes the activity (compare <b>197</b> with <b>189</b> to <b>194</b>). The introduction of a five member heteroaromatic ring, unsubstituted 2-thiophene, displays the best activity (<b>103</b>) followed by 3-furan (<b>188</b>) and 4-thiazone (<b>186</b>). In addition, 1-benzoimidazole (<b>195</b>) also provides better activity than a simple phenyl ring.</p><p>Finally, we studied analogues of the quinazoline core. Replacement of the quinazoline core by purine results in loss of activity, <b>221</b> and <b>222</b>. Elimination of the quinazoline nitrogens also impacts the activity, reducing (<b>207</b>) or completely abolishing it (<b>206</b>). Introduction of one additional nitrogen within position 5 or 8 of the quinazoline ring (<b>208</b> and <b>209</b>) reduced the activity at least 10-fold. Replacement of the quinazoline ring by an unsubstituted pyrimidine ring (<b>210</b>) reduces activity 32-fold, or 10-fold if the pyrimidine is bearing methyl groups in positions 5 and 6 (<b>212</b>). Introduction of a chloro substituent in position 7 of the quinazoline ring abolished activity (compounds <b>213</b> to <b>220</b>).</p><p>In summary, SAR of the series allowed very narrow functional modification, and most of the functionalities of the hit molecule MLS000393962, such us the quinazoline core, the piperidine ring, the sulphonamide substitution and the thiophene hetearomatic ring at the two position were necessary for its activity. Even so, we were able to increase the potency of the molecule to the desirable range. Our most potent compound displays an IC<sub>50</sub> of 320nM, which is comparable with isofagomine which was 80nM in our assay.</p></div></div><div id="ml156.s25"><h3>3.5. Cellular Activity</h3><p>To demonstrate chaperone activity, we measured the capacity of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a> and <a href="/pcsubstance/?term=ML155[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML155</a> to increase the translocation of GC to the lysosome<a class="bibr" href="#ml156.r8" rid="ml156.r8">8</a>, <a class="bibr" href="#ml156.r16" rid="ml156.r16">16</a>, <a class="bibr" href="#ml156.r30" rid="ml156.r30">30</a>, <a class="bibr" href="#ml156.r31" rid="ml156.r31">31</a>. In this experiment, wildtype and mutant fibroblasts were incubated for five days with compound <b>8i</b>, followed by cell fixation and staining with a selective fluorescent GC antibody. Compounds able to promote trafficking from the ER to the lysosome increased the fluorescent lysosomal signal. DMSO and isofagomine were used as negative and positive controls. <a class="figpopup" href="/books/NBK56229/figure/ml156.f2/?report=objectonly" target="object" rid-figpopup="figml156f2" rid-ob="figobml156f2">Figure 2</a> shows the increment of signal in both cell lines that resulted from treatment, confirming the chaperone capacity of these compounds.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml156f2" co-legend-rid="figlgndml156f2"><a href="/books/NBK56229/figure/ml156.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml156f2" rid-ob="figobml156f2"><img class="small-thumb" src="/books/NBK56229/bin/ml156f2.gif" src-large="/books/NBK56229/bin/ml156f2.jpg" alt="Figure 2. Chaperone activity of ML156/CID 9893924/NCGC00159568 and others using wildtype and homozygous, mutant N370S GC fibroblasts." /></a><div class="icnblk_cntnt" id="figlgndml156f2"><h4 id="ml156.f2"><a href="/books/NBK56229/figure/ml156.f2/?report=objectonly" target="object" rid-ob="figobml156f2">Figure 2</a></h4><p class="float-caption no_bottom_margin">Chaperone activity of ML156/CID 9893924/NCGC00159568 and others using wildtype and homozygous, mutant N370S GC fibroblasts. Two genotypes of fibroblasts, fibroblasts homozygous for wildtype GC (top) and fibroblasts homozygous for N370S GC (bottom) were <a href="/books/NBK56229/figure/ml156.f2/?report=objectonly" target="object" rid-ob="figobml156f2">(more...)</a></p></div></div></div><div id="ml156.s26"><h3>3.6. Profiling Assays</h3><div id="ml156.s27"><h4><i>In vitro</i> ADME</h4><p>The result of a microsomal stability study of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID9893924 is shown in <a class="figpopup" href="/books/NBK56229/table/ml156.t10/?report=objectonly" target="object" rid-figpopup="figml156t10" rid-ob="figobml156t10">Table 10</a>. After incubation of the molecule in mouse liver microsomes for 60 minutes in the present of NADPH, 58% of the molecule remained, this suggested that <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID9893924 has a reasonable microsomal stability.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t10"><a href="/books/NBK56229/table/ml156.t10/?report=objectonly" target="object" title="Table 10" class="img_link icnblk_img figpopup" rid-figpopup="figml156t10" rid-ob="figobml156t10"><img class="small-thumb" src="/books/NBK56229/table/ml156.t10/?report=thumb" src-large="/books/NBK56229/table/ml156.t10/?report=previmg" alt="Table 10. Mouse microsomal stability assay at 60 minutes." /></a><div class="icnblk_cntnt"><h4 id="ml156.t10"><a href="/books/NBK56229/table/ml156.t10/?report=objectonly" target="object" rid-ob="figobml156t10">Table 10</a></h4><p class="float-caption no_bottom_margin">Mouse microsomal stability assay at 60 minutes. </p></div></div></div><div id="ml156.s28"><h4><i>In vivo</i> Pharmacokinetic Analysis</h4><p>The pharmacokinetic profiles of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID9893924 in male Swiss Albino mice after intraperitoneal administration twice at a 12 hour interval of CID9893924 at 20mg/kg dose are shown in <a class="figpopup" href="/books/NBK56229/table/ml156.t11/?report=objectonly" target="object" rid-figpopup="figml156t11" rid-ob="figobml156t11">Table 11</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t11"><a href="/books/NBK56229/table/ml156.t11/?report=objectonly" target="object" title="Table 11" class="img_link icnblk_img figpopup" rid-figpopup="figml156t11" rid-ob="figobml156t11"><img class="small-thumb" src="/books/NBK56229/table/ml156.t11/?report=thumb" src-large="/books/NBK56229/table/ml156.t11/?report=previmg" alt="Table 11. Concentrations of CID9893924 in plasma, brain, liver and tail; intraperitoneal administration twice at a 12 hour interval of CID9893924 at 20mg/kg dose in male Swiss Albino Mice (mean and SD)." /></a><div class="icnblk_cntnt"><h4 id="ml156.t11"><a href="/books/NBK56229/table/ml156.t11/?report=objectonly" target="object" rid-ob="figobml156t11">Table 11</a></h4><p class="float-caption no_bottom_margin">Concentrations of CID9893924 in plasma, brain, liver and tail; intraperitoneal administration twice at a 12 hour interval of CID9893924 at 20mg/kg dose in male Swiss Albino Mice (mean and SD). </p></div></div></div></div></div><div id="ml156.s29"><h2 id="_ml156_s29_">4. Discussion</h2><p>In a screen of 326,770 compounds<a class="bibr" href="#ml156.r26" rid="ml156.r26">26</a>, <a class="bibr" href="#ml156.r29" rid="ml156.r29">29</a>, we found several series of GC inhibitors. NCGC00182292, which was one of the most potent compounds in the series, was further characterized in a variety of GC assay formats. Most notable was weak or a complete lack of activity in assays with purified, reconstituted GC protein (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/AID2597" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID2597</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2595" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2595</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2596" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2596</a>). These assays lacked saposin C, an endogenous regulator of GC activity in cells, and so it is unclear how relevant these results are. Unfortunately, GC cleavage of glycosylceramide, the native substrate of GC, can only be examined in purified assay systems, and so it is unknown if this series inhibits cleavage of the native substrate. However, this might be an advantage for a chemical chaperone, as it is preferred that a chaperone does not interfere with substrate processing once protein is translocated to the lysosome.</p><p>Among the hits, also a thiourea singleton, NCGC159568 (<b>8i</b>), was confirmed. This compound was inactive against the related sugar hydrolases alpha-glucosidase and alpha-galactosidase at a 50μM concentration, and did not exhibit auto-fluorescence. In addition, the compound had very similar activity against GC as determined using an alternate resorufin-based substrate, thereby ruling out nonspecific effects on the fluorescent reporter. More importantly, the chaperone capacity of this compound was confirmed in a translocation assay, in which treatment of compound <b>8i</b> resulted in increase of GC translocation to the lysosome. Thus, we initiated a structure-activity relationship (SAR) study around the hit compound, as shown in <a class="figpopup" href="/books/NBK56229/figure/ml156.f3/?report=objectonly" target="object" rid-figpopup="figml156f3" rid-ob="figobml156f3">Figure 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml156f3" co-legend-rid="figlgndml156f3"><a href="/books/NBK56229/figure/ml156.f3/?report=objectonly" target="object" title="Figure 3" class="img_link icnblk_img figpopup" rid-figpopup="figml156f3" rid-ob="figobml156f3"><img class="small-thumb" src="/books/NBK56229/bin/ml156f3.gif" src-large="/books/NBK56229/bin/ml156f3.jpg" alt="Figure 3. Structure-activity relationship (SAR) study for CID 9893924 (8i)." /></a><div class="icnblk_cntnt" id="figlgndml156f3"><h4 id="ml156.f3"><a href="/books/NBK56229/figure/ml156.f3/?report=objectonly" target="object" rid-ob="figobml156f3">Figure 3</a></h4><p class="float-caption no_bottom_margin">Structure-activity relationship (SAR) study for CID 9893924 (<i>8i</i>). </p></div></div><p>As described in <a href="#ml156.s23">section 3.4</a>, several positions of the molecule were explored and preliminary structure-activity relationships were obtained for the inhibitory activity. Since <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924 is a known agonist of the Somatostatin receptor sst4, several analogs were tested in a human SST4 receptor binding assay. As shown in the <a class="figpopup" href="/books/NBK56229/table/ml156.t12/?report=objectonly" target="object" rid-figpopup="figml156t12" rid-ob="figobml156t12">Table 12</a>, the inhibitory activity observed in the N370S spleen homogenate assay was not correlated with the activity in the SST4 binding assay. For example, compound <b>24</b> is about 10-fold more potent than compound <b>27</b> in the N370S spleen homogenate assay, but <b>24</b> is about 5 fold less potent than <b>27</b> in the SSt4 binding assay. These results suggested that the SSt4 activity of this series could be removed without diminishing the GC activity through further structure modification.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml156t12"><a href="/books/NBK56229/table/ml156.t12/?report=objectonly" target="object" title="Table 12" class="img_link icnblk_img figpopup" rid-figpopup="figml156t12" rid-ob="figobml156t12"><img class="small-thumb" src="/books/NBK56229/table/ml156.t12/?report=thumb" src-large="/books/NBK56229/table/ml156.t12/?report=previmg" alt="Table 12. Comparison of GC inhibitory activities with Somatostatin receptor sst4 activity." /></a><div class="icnblk_cntnt"><h4 id="ml156.t12"><a href="/books/NBK56229/table/ml156.t12/?report=objectonly" target="object" rid-ob="figobml156t12">Table 12</a></h4><p class="float-caption no_bottom_margin">Comparison of GC inhibitory activities with Somatostatin receptor sst4 activity. </p></div></div><p><a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924 has demonstrated chaperone activity, and preliminary pharmacokinetic studies have demonstrated that the molecule has good exposure in plasma, brain and liver upon IP administration. Exposure in brain is especially significant, as the current standard-of-care, enzyme replacement therapy, has no effect on the neurological component of the disease. In addition, at this high dose, the compound did not exhibit any acute toxicity in initial testing. Thus, this molecule will be tested <i>in vivo</i> for the proof of principle study.</p><div id="ml156.s30"><h3>4.1. Comparison to existing art and how the new probe is an improvement</h3><p>As it has been previously mentioned in the introduction, currently described GC chaperone molecules are based on an aminosugar scaffold. The current series presents a new template with very good selectivity versus other glycosidases. In addition, it seems that our series has a lower capacity than isofagomine to inhibit hydrolysis of ceramides maintaining similar chaperone capacity, and therefore it could be expected that there is a potentially better therapeutic window for the series.</p></div><div id="ml156.s31"><h3>4.2. Mechanism of Action Studies</h3><p>In enzyme kinetics assays, the probe, along with other glucocerebrosidase inhibitors such as isofagomine, demonstrated mixed mode inhibition – neither competitive nor non-competitive enzyme kinetics. Obviously, from x-ray crystal structure studies of isofagomine binding, the compound binds in the active site. Thus, the current homogenate-based assays might be ill-suited for such kinetic characterization.</p></div><div id="ml156.s32"><h3>4.3. Planned Future Studies</h3><p>Preliminary pharmacokinetic studies demonstrated that <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924 has very good exposure in plasma, brain and liver upon IP administration at a 12 hour interval of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924 at 20mg/kg dose. We are planning to test this molecule in an animal model for a proof of principle study. In this study, we will dose wt and mutant GC animals for seven days with our inhibitor. After that period, we will stop the treatment with our compound, and sacrifice animals at several time points (1, 2 and 3 days) after treatment to allow the drug to be eliminated. Relevant tissues (blood, liver, brain) will be collected and GC specific activity will be measured. Compounds able to increase the translocation must increase the overall GC production, and therefore should increase the GC specific activity. Upon confirmation in the <i>in vivo</i> study, further SAR studies will be preformed to remove the Somatostatin receptor sst4 activity.</p></div></div><div id="ml156.rl1"><h2 id="_ml156_rl1_">5 References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ml156.r1">Grabowski G. Phenotype, diagnosis, and treatment of Gaucher’s disease. <span><span class="ref-journal">The Lancet. </span>2008;<span class="ref-vol">372</span>(9645):1263–1271.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19094956" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19094956</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ml156.r2">Sawkar AR, D’Haeze W, Kelly JW. Therapeutic strategies to ameliorate lysosomal storage disorders – a focus on Gaucher disease. <span><span class="ref-journal">Cell. Mol. Life Sci. </span>2006;<span class="ref-vol">63</span>:1179–1192.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16568247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16568247</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ml156.r3">Wedeking A, van Echten-Deckert G. Glycosphingolipid Structure and Function in Membranes. <span><span class="ref-journal">Curr. Org. Chem. </span>2007;<span class="ref-vol">11</span>(7):579–589.</span></div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ml156.r4">Hruska KS, LaMarca ME, Sidransky E. <span class="ref-journal">Gaucher Disease.</span> Futerman AH, Zimran A, editors. CRC Press; Boca Raton, FL: 2006. p. 13.</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ml156.r5">Futerman AH, van Meer G. The Cell Biology of Lysosomal Storage Disorders. <span><span class="ref-journal">Nat. Rev. Mol. Cell. Biol. </span>2004;<span class="ref-vol">5</span>:554–565.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15232573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15232573</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ml156.r6">Barton NW, Brady RO, Dambrosia JM, Dibisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher’s disease. <span><span class="ref-journal">N. Engl. J. Med. </span>1991;<span class="ref-vol">324</span>:1464–1470.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/2023606" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2023606</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ml156.r7">Butters TD. Pharmacotherapeutic strategies using small molecules for the treatment of glycolipid lysosomal storage disorders. <span><span class="ref-journal">Expert Opin. Pharmacother. </span>2007;<span class="ref-vol">8</span>:427–435.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17309337" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17309337</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="ml156.r8">Sawker AR, Cheng W-C, Beutler W, Wong C-H, Balch WE, Kelly JW. Chemical chaperones increase the cellular activity of N370S β-glucosidase: A therapeutic strategy for Gaucher disease. <span><span class="ref-journal">Proc. Natl. Acad. Sci. U.S.A. </span>2002;<span class="ref-vol">99</span>:15428–15433.</span> [<a href="/pmc/articles/PMC137733/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC137733</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12434014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12434014</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="ml156.r9">Sawker AR, Adamski-Werner SL, Cheng W-C, Wong C-H, Beutler E, Zimmer K-P, Kelly JW, Gaucher Disease-Associated Glucocerebrosidases Show Mutation-Dependent Chemical Chaperoning Profiles. <span><span class="ref-journal">Chem. Biol. </span>2005;<span class="ref-vol">12</span>:1235–1244.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16298303" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16298303</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="ml156.r10">Yu Z, Sawker AR, Whalen LJ, Wong C-H, Kelly JW. Isofagomine- and 2,5-Anhydro-2,5-imino-d-glucitol-Based Glucocerebrosidase Pharmacological Chaperones for Gaucher Disease Intervention. <span><span class="ref-journal">J. Med. Chem. </span>2007;<span class="ref-vol">50</span>(10):94–100.</span> [<a href="/pmc/articles/PMC2543937/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2543937</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17201413" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17201413</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="ml156.r11">Wennekes T, van der Berg RJBHN, Donker W, van der Marel GA, Strijland A, Aerts JMFG, Overkleeft HS. Development of Adamantan-1-yl-methoxy-Functionalized 1-Deoxynojirimycin Derivatives as Selective Inhibitors of Glucosylceramide Metabolism in Man. <span><span class="ref-journal">J. Org. Chem. </span>2007;<span class="ref-vol">72</span>(4):1088–1097.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17243712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17243712</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="ml156.r12">Zhu X, Sheth KA, Li S, Chang H-H, Fan J-Q. Rational Design and Synthesis of Highly Potent Beta-Glucocerebrosidase Inhibitors. <span><span class="ref-journal">Angew. Chem. Int. Ed. Engl. </span>2005;<span class="ref-vol">44</span>(45):7450–7453.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16231389" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16231389</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="ml156.r13">Butters TD, Dwek RA, Platt FM. Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses. <span><span class="ref-journal">Glycobiology. </span>2005;<span class="ref-vol">15</span>:43R–52R.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15901676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15901676</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="ml156.r14">Chang HH, Asano N, Ishii S, Ichikawa Y, Fan JQ. Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients. <span><span class="ref-journal">FEBS J. </span>2006;<span class="ref-vol">273</span>(17):4082–4092.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16934036" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16934036</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="ml156.r15">Compain P, Martin OR, Boucheron C, Godin G, Yu L, Ikeda K, Asano N. Design and Synthesis of Highly Potent and Selective Pharmacological Chaperones for the Treatment of Gaucher’s disease. <span><span class="ref-journal">ChemBioChem. </span>2006;<span class="ref-vol">7</span>(9):1356–1359.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16871601" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16871601</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="ml156.r16">Sawkar AR, Schmitz M, Zimmer KP, Reczek D, Edmunds T, Balch WE, Kelly JW. Chemical Chaperones and Permissive Temperatures Alter the Cellular Localization of Gaucher Disease Associated Glucocerebrosidase Variants. <span><span class="ref-journal">ACS Chem Biol. </span>2006;<span class="ref-vol">1</span>(4):235–251.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17163678" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17163678</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="ml156.r17">Steet RA, Chung S, Wustman B, Powe A, Do H, Kornfeld SA. The iminosugar isofagomine increases the activity of N370S mutant acid β-glucosidase in Gaucher fibroblasts by several mechanisms. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>2006;<span class="ref-vol">103</span>:13813–13818.</span> [<a href="/pmc/articles/PMC1564243/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1564243</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16945909" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16945909</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="ml156.r18">Yu L, Ikeda K, Kato A, Adachi I, Godin G, Compain P, Martin O, Asano N. α-1-C-Octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease. <span><span class="ref-journal">Bioorg Med Chem. </span>2006;<span class="ref-vol">14</span>(23):7736–7744.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16919960" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16919960</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="ml156.r19">Egido-Gabas M, Canals D, Casas J, Llebaria A, Delgado A. Aminocyclitols as Pharmacological Chaperones for Glucocerebrosidase, a Defective Enzyme in Gaucher Disease. <span><span class="ref-journal">ChemMedChem. </span>2007;<span class="ref-vol">2</span>(7):992–994.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17479993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17479993</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="ml156.r20">Lei K, Ninomiya H, Suzuki M, Inoue T, Sawa M, Iida M, Ida H, Eto Y, Ogawa S, Ohno K, Suzuki Y. Enzyme enhancement activity of N-octyl-beta-valienamine on beta-glucosidase mutants associated with Gaucher disease. <span><span class="ref-journal">Biochim Biophys Acta. </span>2007;<span class="ref-vol">1772</span>(5):587–596.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17363227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17363227</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="ml156.r21"> <a href="http://clinicaltrials.gov/ct2/show/NCT00358150" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://clinicaltrials.gov/ct2/show/NCT00358150</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="ml156.r22"> <a href="http://ir.amicustherapeutics.com/ReleaseDetail.cfm?ReleaseID=413437" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://ir<wbr style="display:inline-block"></wbr>​.amicustherapeutics<wbr style="display:inline-block"></wbr>​.com/ReleaseDetail<wbr style="display:inline-block"></wbr>​.cfm?ReleaseID=413437</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="ml156.r23">Fan JQ. A contradictory treatment for lysosomal storage disorders: inhibitors enhance mutant enzyme activity. <span><span class="ref-journal">Trends Pharmacol Sci. </span>2003;<span class="ref-vol">24</span>(7):355–360.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12871668" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12871668</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="ml156.r24">Wustman Brandon. (Amicus therapeutics). <span class="ref-journal">Personal communication.</span> </div></dd></dl><dl class="bkr_refwrap"><dt>25.</dt><dd><div class="bk_ref" id="ml156.r25">John M, Wendeler M, Heller M, Sandhoff K, Kessler H. Characterization of Human Saposins by NMR Spectroscopy. <span><span class="ref-journal">Biochemistry. </span>2006;<span class="ref-vol">45</span>(16):5206–5216.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16618109" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16618109</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>26.</dt><dd><div class="bk_ref" id="ml156.r26">Zheng W, Padia J, Urban DJ, Jadhav A, Goker-Alpan O, Simeonov A, Goldin E, Auld D, LaMarca ME, Inglese J, Austin CP, Sidransky E. Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease. <span><span class="ref-journal">Proc. Natl. Acad. Sci. U.S.A. </span>2007;<span class="ref-vol">104</span>:13192.</span> [<a href="/pmc/articles/PMC1936979/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1936979</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17670938" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17670938</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>27.</dt><dd><div class="bk_ref" id="ml156.r27">We evaluated several tissues finding that the spleen has one of the highest levels of GC activity.</div></dd></dl><dl class="bkr_refwrap"><dt>28.</dt><dd><div class="bk_ref" id="ml156.r28">Goker-Alpan O, Lopez G, Vithayathil J, Davis J, Hallet M, Sidransky E. The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations. <span><span class="ref-journal">Arch Neurol. </span>2008;<span class="ref-vol">65</span>(10):1353–1357.</span> [<a href="/pmc/articles/PMC2629407/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2629407</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18852351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18852351</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>29.</dt><dd><div class="bk_ref" id="ml156.r29">Inglese J, Auld DS, Jadhav A, Johnson RL, Simeonov A, Yasgar A, Zheng W, Austin CP. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>2006;<span class="ref-vol">103</span>(31):11473–11478.</span> [<a href="/pmc/articles/PMC1518803/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1518803</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16864780" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16864780</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>30.</dt><dd><div class="bk_ref" id="ml156.r30">Schmitz M, Alfalah M, Aerts JM, Naim HY, Zimmer KP. Impaired trafficking of mutants of lysosomal glucocerebrosidase in Gaucher’s disease. <span><span class="ref-journal">Int J Biochem Cell Biol. </span>2005;<span class="ref-vol">37</span>(11):2310–2320.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15982918" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15982918</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>31.</dt><dd><div class="bk_ref" id="ml156.r31">Lieberman RL, Wustman BA, Huertas P, Powe AC Jr, Pine CW, Khanna R, Schlossmacher MG, Ringe D, Petsko GA. Structure of acid -glucosidase with pharmacological chaperone provides insight into Gaucher disease. <span><span class="ref-journal">Nat Chem Biol. </span>2007;<span class="ref-vol">3</span>(2):101–107.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17187079" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17187079</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK56229_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Omid Motabar</span>,<sup>A</sup> <span itemprop="author">Wenwei Huang</span>,<sup>B</sup> <span itemprop="author">Juan Jose Marugan</span>,<sup>B</sup> <span itemprop="author">Noel Southall</span>,<sup>B</sup> <span itemprop="author">Maria DeBernardi</span>,<sup>A</sup> <span itemprop="author">Wei Zheng</span>,<sup>B</sup> and <span itemprop="author">Ellen Sidransky</span><sup>A</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>A</sup>
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Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 35 Convent Drive, MSC 3708, Bethesda, MD 20894-3708, USA</div><div class="affiliation"><sup>B</sup>
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NIH Chemical Genomics Center, 9800 Medical Center Dr., Building B, Bethesda, MD, 20892-3370</div><h3>Publication History</h3><p class="small">Received: <span itemprop="datePublished">March 24, 2010</span>; Last Update: <span itemprop="dateModified">March 25, 2011</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>Motabar O, Huang W, Marugan JJ, et al. Identification of Modulators of the N370S Mutant Form of Glucocerebrosidase as a Potential Therapy for Gaucher Disease - Chemotype 2. 2010 Mar 24 [Updated 2011 Mar 25]. 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/ml157/?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/ml155/?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="figobml156fu1"><div id="ml156.fu1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu1.jpg" alt="ML156." /></div><h3><span class="title"><a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a></span></h3></div></article><article data-type="table-wrap" id="figobml156tu1"><div id="ml156.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml156.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID/ML#</th><th id="hd_h_ml156.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Target Name</th><th id="hd_h_ml156.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC<sub>50</sub>/EC<sub>50</sub> (nM) [SID, AID]</th><th id="hd_h_ml156.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_ml156.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC<sub>50</sub>/EC<sub>50</sub> (μM) [SID, AID]</th><th id="hd_h_ml156.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Fold Selective</th><th id="hd_h_ml156.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Secondary Assay(s) Name: IC<sub>50</sub>/EC<sub>50</sub> (nM) [SID, AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml156.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9893924/<a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a></td><td headers="hd_h_ml156.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">580nM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449177" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449177</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2590</a>]</td><td headers="hd_h_ml156.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Alpha-glucosidase<br /><br />Alpha-galactosidase</td><td headers="hd_h_ml156.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">> 57μM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/2921544" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2921544</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2577</a>]<br /><br />> 57μM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/2921544" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2921544</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2578</a>]</td><td headers="hd_h_ml156.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">>100-fold</td><td headers="hd_h_ml156.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chaperone activity in N370S GC fibroblasts: 500nM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/2921544" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2921544</a>,<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2587" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2587</a>]</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t1"><div id="ml156.t1" class="table"><h3><span class="label">Table 1</span><span class="title">Assay protocols and data deposited into PubChem</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t1_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PubChem AID</th><th id="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type</th><th id="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Target</th><th id="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conc. Range</th><th id="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Samples Tested</th><th id="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Notes</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2101</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primary qHTS</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.5μM – 0.7nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">326,770</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tissue, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2590" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2590</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Confirmatory</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54μM – 0.01nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">320</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tissue, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2613" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2613</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.5μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">83</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tissue, red</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2592" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2592</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wildtype GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.5μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tissue, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2588" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2588</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wildtype GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50μM – 0.1nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">152</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tissue, red</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2595" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2595</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wildtype GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2597" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2597</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2596" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2596</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">230μM – 0.1nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">94</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified, natural substrate</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2577</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anti-target</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Alpha-glucosidase</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.5μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2578</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anti-target</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Alpha-galactosidase</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.5μM – 0.3nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified, blue</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2587" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2587</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tertiary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100μM – 10nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Immunostaining of fibroblast lysosomes</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2589" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2589</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tertiary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wildtype GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100μM – 10nM</td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Immunostaining of fibroblast lysosomes</td></tr><tr><td headers="hd_h_ml156.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2593" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2593</a></td><td headers="hd_h_ml156.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Summary</td><td headers="hd_h_ml156.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N370S GC</td><td headers="hd_h_ml156.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ml156.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_ml156.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t2"><div id="ml156.t2" class="table"><h3><span class="label">Table 2</span><span class="title">Compounds submitted to the MLSMR</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS</th><th id="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">SID</th><th id="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">CID</th><th id="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">NCGC ID</th><th id="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">ML</th><th id="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Type</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703100</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495629" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495629</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9893924</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00159568-02</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Probe</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703117</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495645" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495645</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820550</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00185835-02</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703118</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495646" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495646</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820554</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00185837-02</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703119</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495647" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495647</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820562</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00185839-02</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703106</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495635" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495635</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820570</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187945-01</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703107</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495636" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495636</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820542</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187954-01</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr><tr><td headers="hd_h_ml156.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS002703108</td><td headers="hd_h_ml156.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99495637" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">99495637</a></td><td headers="hd_h_ml156.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44820564</td><td headers="hd_h_ml156.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187957-01</td><td headers="hd_h_ml156.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml156.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analog</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml156f4"><div id="ml156.f4" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f4.jpg" alt="Scheme 1. Synthesis of compounds 8a-l." /></div><h3><span class="label">Scheme 1</span><span class="title">Synthesis of compounds 8a-l</span></h3><div class="caption"><p>Reagents and conditions: (i) H<sub>2</sub>N(CH<sub>2</sub>)<sub>n</sub>NH<sub>2</sub> (<b>2</b>), pyridine, refluxed; (ii) TrCl, THF, Et<sub>3</sub>N, 0 °C-r.t.; (iii) THF, LiHMDS, R<sub>1</sub>X, r.t.; (iv) TFA, DCM; (v) <i>i</i>PrNEt<sub>2</sub>, <b>7</b>, 1,1′-thiocarbonyldiimidazole (or 1,1′-carbonyldiimidazole), DCM, MW 130 °C; (vi) TFA, DCM</p></div></div></article><article data-type="fig" id="figobml156f5"><div id="ml156.f5" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f5.jpg" alt="Scheme 2. Synthesis of compound 10." /></div><h3><span class="label">Scheme 2</span><span class="title">Synthesis of compound 10</span></h3><div class="caption"><p>Reagents and conditions: (i) PhB(OH)<sub>2</sub>, Na<sub>2</sub>CO<sub>3</sub>, Pd(PPh<sub>3</sub>)<sub>4</sub>, 100 °C, 2 h; (ii) TFA, DMC; (iii) <i>i</i>PrNEt<sub>2</sub>, <b>7a</b>, 1,1′-thiocarbonyldimididazole, DCM, MW 150 °C, 10 min; (iv) TFA</p></div></div></article><article data-type="fig" id="figobml156f6"><div id="ml156.f6" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f6.jpg" alt="Scheme 3. Syntheses of compounds 13a-b." /></div><h3><span class="label">Scheme 3</span><span class="title">Syntheses of compounds 13a-b</span></h3><div class="caption"><p>Reagents and conditions: (i) <i>i</i>PrNEt<sub>2</sub>, <b>11</b>, 1,1′-thiocarbonyldimididazole, DCM, MW 130 °C, 10 min; (ii) TFA; (iii) for <b>13b</b> CH<sub>3</sub>COCl</p></div></div></article><article data-type="fig" id="figobml156fu2"><div id="ml156.fu2" class="figure"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu2.jpg" alt="Image ml156fu2" /></div></div></article><article data-type="fig" id="figobml156fu3"><div id="ml156.fu3" class="figure"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu3.jpg" alt="Image ml156fu3" /></div></div></article><article data-type="fig" id="figobml156fu4"><div id="ml156.fu4" class="figure"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu4.jpg" alt="Image ml156fu4" /></div></div></article><article data-type="fig" id="figobml156fu5"><div id="ml156.fu5" class="figure"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu5.jpg" alt="Image ml156fu5" /></div></div></article><article data-type="fig" id="figobml156fu6"><div id="ml156.fu6" class="figure"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156fu6.jpg" alt="Image ml156fu6" /></div></div></article><article data-type="table-wrap" id="figobml156t3"><div id="ml156.t3" class="table"><h3><span class="label">Table 3</span><span class="title">Compound representatives of initial hit series</span></h3><div class="caption"><p>Isofagomine is an imino sugar previously reported to chaperone glucocerebrosidase. NCGC00092410 is a non-imino sugar previously reported to inhibit purified glucocerebrosidase.</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t3_lrgtbl__"><table><thead><tr><th id="hd_h_ml156.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Compound</th><th id="hd_h_ml156.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Series (PubChem CID)</th><th id="hd_h_ml156.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type</th><th id="hd_h_ml156.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified N370S</th><th id="hd_h_ml156.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Purified WT</th><th id="hd_h_ml156.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Spleen N370S</th><th id="hd_h_ml156.t3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Spleen WT</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Isofagomine</td><td headers="hd_h_ml156.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">447607</td><td headers="hd_h_ml156.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inhibitor</td><td headers="hd_h_ml156.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50–60nM</td><td headers="hd_h_ml156.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10–15nM</td><td headers="hd_h_ml156.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70–80nM</td><td headers="hd_h_ml156.t3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100nM</td></tr><tr><td headers="hd_h_ml156.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NCGC00092410</td><td headers="hd_h_ml156.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quinoline<br /><br />5067281</td><td headers="hd_h_ml156.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inhibitor</td><td headers="hd_h_ml156.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">560–1000nM</td><td headers="hd_h_ml156.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70–80nM</td><td headers="hd_h_ml156.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">> 10μM</td><td headers="hd_h_ml156.t3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">> 10μM</td></tr><tr><td headers="hd_h_ml156.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MLS000393962</td><td headers="hd_h_ml156.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quinazoline<br /><br />2477651</td><td headers="hd_h_ml156.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inhibitor</td><td headers="hd_h_ml156.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inactive</td><td headers="hd_h_ml156.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.6–2.5μM</td><td headers="hd_h_ml156.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">450nM</td><td headers="hd_h_ml156.t3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1000nM</td></tr><tr><td headers="hd_h_ml156.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NCGC00159568</td><td headers="hd_h_ml156.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Thiourea<br /><br />9893924</td><td headers="hd_h_ml156.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inhibitor</td><td headers="hd_h_ml156.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2500μM</td><td headers="hd_h_ml156.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">710nM</td><td headers="hd_h_ml156.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">580nM</td><td headers="hd_h_ml156.t3_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">350nM</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml156f1"><div id="ml156.f1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f1.jpg" alt="Figure 1. Concentration-response of probe, CID 9893924/ML156, in primary screening assay for N370S GC inhibition from tissue homogenate." /></div><h3><span class="label">Figure 1</span><span class="title">Concentration-response of probe, CID 9893924/<a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>, in primary screening assay for N370S GC inhibition from tissue homogenate</span></h3><div class="caption"><p>Compound IC<sub>50</sub>, measured in triplicate on three different days, was 580 +/− 30nM.</p></div></div></article><article data-type="table-wrap" id="figobml156t4"><div id="ml156.t4" class="table"><h3><span class="label">Table 4</span><span class="title">Structure activity relationship (SAR)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t4_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml156.t4_1_1_1_1" colspan="13" rowspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu7.jpg" alt="Image ml156fu7.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Entry</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cmpd. No.</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC ID</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><sup>*</sup></th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R3</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">n</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">X</th><th headers="hd_h_ml156.t4_1_1_1_1" id="hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AC50</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8i</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9893924</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/29215544" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">29215544</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00159568-01</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.6±0.1</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8i</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9893924</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449177" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449177</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00159568-02</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.6±0.1</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8a</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820550</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449189" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449189</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185835</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.2</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8f</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820562</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449191" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449191</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185837</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Butyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.2</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8h</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820554</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449193" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449193</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185839</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Benzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.8</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8g</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820544</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449192" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449192</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185838</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">46.0</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8b</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820546</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449194" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449194</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185840</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7.3</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>10</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820557</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449208" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449208</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187953</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Ph</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.3</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8c</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820553</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449213" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449213</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187959</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Ph</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.0</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8d</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10554498</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449195" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449195</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185841</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.1</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8e</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820570</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449200" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449200</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187945</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.8</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8l</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820548</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449197" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449197</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185843</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">18.3</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8j</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5311371</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449196" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449196</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185842</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">O</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.6</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8k</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820568</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449205" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449205</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187950</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">O</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>13a</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820542</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449209" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449209</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187954</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NH2</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">45.0</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>13b</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820564</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449212" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449212</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187957</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Chlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NHCOCH3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">inactive</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>25</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820567</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449198" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449198</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00185844</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3,4-Dichlorobenzyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CH3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">inactive</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">18</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8q</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820543</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449210" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449210</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187955</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">phenylethyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.8</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">19</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8m</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820565</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449201" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449201</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187946</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-chlorophenylethyl</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5-Br</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4-Imidazole</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">20</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>26</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820569</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449202" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449202</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187947</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.8</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">21</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>27</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820563</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449204" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449204</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187949</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">18</td></tr><tr><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">22</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>24</b></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">44820545</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449203" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449203</a></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC00187948</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml156.t4_1_1_1_1 hd_h_ml156.t4_1_1_2_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.3</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="ml156.tfn1"><p class="no_margin">P = purchased S = synthesized</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml156t5"><div id="ml156.t5" class="table"><h3><span class="label">Table 5</span><span class="title">Analogs with sulfonamide aromatic modifications having a phenyl at two positions</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t5_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t5_1_1_1_1" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu8.jpg" alt="Image ml156fu8.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t5_1_1_1_1" id="hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound number</th><th headers="hd_h_ml156.t5_1_1_1_1" id="hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t5_1_1_1_1" id="hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N370S<br />AC<sub>50</sub>(μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>72</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu9.jpg" alt="Image ml156fu9.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>73</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu10.jpg" alt="Image ml156fu10.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>74</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu11.jpg" alt="Image ml156fu11.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>75</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu12.jpg" alt="Image ml156fu12.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>76</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu13.jpg" alt="Image ml156fu13.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>77</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu14.jpg" alt="Image ml156fu14.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.95</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>78</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu15.jpg" alt="Image ml156fu15.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.08</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>79</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu16.jpg" alt="Image ml156fu16.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50.45</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>80</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu17.jpg" alt="Image ml156fu17.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.95</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>81</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu18.jpg" alt="Image ml156fu18.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>82</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu19.jpg" alt="Image ml156fu19.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>83</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu20.jpg" alt="Image ml156fu20.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>84</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu21.jpg" alt="Image ml156fu21.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.99</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>85</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu22.jpg" alt="Image ml156fu22.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>86</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu23.jpg" alt="Image ml156fu23.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>87</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu24.jpg" alt="Image ml156fu24.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>88</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu25.jpg" alt="Image ml156fu25.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.08</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>89</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu26.jpg" alt="Image ml156fu26.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>90</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu27.jpg" alt="Image ml156fu27.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>91</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu28.jpg" alt="Image ml156fu28.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40.07</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>92</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu29.jpg" alt="Image ml156fu29.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.08</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>93</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu30.jpg" alt="Image ml156fu30.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31.83</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>94</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu31.jpg" alt="Image ml156fu31.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>95</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu32.jpg" alt="Image ml156fu32.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.85</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>96</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu33.jpg" alt="Image ml156fu33.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>97</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu34.jpg" alt="Image ml156fu34.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>98</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu35.jpg" alt="Image ml156fu35.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.35</td></tr><tr><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>99</b></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu36.jpg" alt="Image ml156fu36.jpg" /></div></td><td headers="hd_h_ml156.t5_1_1_1_1 hd_h_ml156.t5_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t6"><div id="ml156.t6" class="table"><h3><span class="label">Table 6</span><span class="title">Analogs with sulfonamide aromatic modifications having a thiophene at two positions</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t6_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t6_1_1_1_1" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu37.jpg" alt="Image ml156fu37.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t6_1_1_1_1" id="hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound number</th><th headers="hd_h_ml156.t6_1_1_1_1" id="hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t6_1_1_1_1" id="hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N370S<br />AC<sub>50</sub>(μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>100</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu38.jpg" alt="Image ml156fu38.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.26</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>101</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu39.jpg" alt="Image ml156fu39.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>102</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu40.jpg" alt="Image ml156fu40.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.52</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>103</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu41.jpg" alt="Image ml156fu41.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.32</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>104</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu42.jpg" alt="Image ml156fu42.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.80</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>105</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu43.jpg" alt="Image ml156fu43.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.59</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>106</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu44.jpg" alt="Image ml156fu44.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>107</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu45.jpg" alt="Image ml156fu45.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>108</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu46.jpg" alt="Image ml156fu46.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.40</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>109</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu47.jpg" alt="Image ml156fu47.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>110</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu48.jpg" alt="Image ml156fu48.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>111</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu49.jpg" alt="Image ml156fu49.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>112</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu50.jpg" alt="Image ml156fu50.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>113</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu51.jpg" alt="Image ml156fu51.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>114</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu52.jpg" alt="Image ml156fu52.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>115</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu53.jpg" alt="Image ml156fu53.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>116</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu54.jpg" alt="Image ml156fu54.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.59</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>117</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu55.jpg" alt="Image ml156fu55.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>118</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu56.jpg" alt="Image ml156fu56.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.01</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>119</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu57.jpg" alt="Image ml156fu57.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>120</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu58.jpg" alt="Image ml156fu58.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.52</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>121</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu59.jpg" alt="Image ml156fu59.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.52</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>122</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu60.jpg" alt="Image ml156fu60.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>123</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu61.jpg" alt="Image ml156fu61.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.26</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>124</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu62.jpg" alt="Image ml156fu62.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.63</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>125</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu63.jpg" alt="Image ml156fu63.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.99</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>126</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu64.jpg" alt="Image ml156fu64.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>127</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu65.jpg" alt="Image ml156fu65.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>128</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu66.jpg" alt="Image ml156fu66.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>129</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu67.jpg" alt="Image ml156fu67.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>130</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu68.jpg" alt="Image ml156fu68.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.04</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>131</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu69.jpg" alt="Image ml156fu69.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.32</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>132</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu70.jpg" alt="Image ml156fu70.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.80</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>133</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu71.jpg" alt="Image ml156fu71.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>134</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu72.jpg" alt="Image ml156fu72.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>135</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu73.jpg" alt="Image ml156fu73.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.01</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>136</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu74.jpg" alt="Image ml156fu74.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.59</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>136</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu75.jpg" alt="Image ml156fu75.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.35</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>138</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu76.jpg" alt="Image ml156fu76.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>139</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu77.jpg" alt="Image ml156fu77.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>140</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu78.jpg" alt="Image ml156fu78.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.04</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>141</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu79.jpg" alt="Image ml156fu79.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.00</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>142</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu80.jpg" alt="Image ml156fu80.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>143</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu81.jpg" alt="Image ml156fu81.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>144</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu82.jpg" alt="Image ml156fu82.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.33</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>145</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu83.jpg" alt="Image ml156fu83.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.01</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>146</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu84.jpg" alt="Image ml156fu84.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.50</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>147</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu85.jpg" alt="Image ml156fu85.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.50</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>148</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu86.jpg" alt="Image ml156fu86.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.59</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>149</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu87.jpg" alt="Image ml156fu87.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.26</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>150</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu88.jpg" alt="Image ml156fu88.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>151</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu89.jpg" alt="Image ml156fu89.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.01</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>152</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu90.jpg" alt="Image ml156fu90.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.50</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>153</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu91.jpg" alt="Image ml156fu91.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.26</td></tr><tr><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>154</b></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu92.jpg" alt="Image ml156fu92.jpg" /></div></td><td headers="hd_h_ml156.t6_1_1_1_1 hd_h_ml156.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.01</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t7"><div id="ml156.t7" class="table"><h3><span class="label">Table 7</span><span class="title">Analogues with the modifications at the linker</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t7_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t7_1_1_1_1" colspan="4" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu93.jpg" alt="Image ml156fu93.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t7_1_1_1_1" id="hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound number</th><th headers="hd_h_ml156.t7_1_1_1_1" id="hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t7_1_1_1_1" id="hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml156.t7_1_1_1_1" id="hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N370S<br />AC50 (μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>103</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu94.jpg" alt="Image ml156fu94.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu95.jpg" alt="Image ml156fu95.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.32</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>165</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu96.jpg" alt="Image ml156fu96.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu97.jpg" alt="Image ml156fu97.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.52</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>166</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu98.jpg" alt="Image ml156fu98.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu99.jpg" alt="Image ml156fu99.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.52</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>167</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu100.jpg" alt="Image ml156fu100.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu101.jpg" alt="Image ml156fu101.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50.45</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>168</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu102.jpg" alt="Image ml156fu102.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu103.jpg" alt="Image ml156fu103.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.00</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>169</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu104.jpg" alt="Image ml156fu104.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu105.jpg" alt="Image ml156fu105.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.04</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>170</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu106.jpg" alt="Image ml156fu106.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu107.jpg" alt="Image ml156fu107.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50.45</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>171</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu108.jpg" alt="Image ml156fu108.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu109.jpg" alt="Image ml156fu109.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">79.98</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>172</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu110.jpg" alt="Image ml156fu110.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu111.jpg" alt="Image ml156fu111.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.96</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>173</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu112.jpg" alt="Image ml156fu112.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu113.jpg" alt="Image ml156fu113.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50.45</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>174</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu114.jpg" alt="Image ml156fu114.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu115.jpg" alt="Image ml156fu115.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10.07</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>175</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu116.jpg" alt="Image ml156fu116.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu117.jpg" alt="Image ml156fu117.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.00</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>176</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu118.jpg" alt="Image ml156fu118.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu119.jpg" alt="Image ml156fu119.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>177</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu120.jpg" alt="Image ml156fu120.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu121.jpg" alt="Image ml156fu121.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">79.98</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>178</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu122.jpg" alt="Image ml156fu122.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu123.jpg" alt="Image ml156fu123.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>179</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu124.jpg" alt="Image ml156fu124.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu125.jpg" alt="Image ml156fu125.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.35</td></tr><tr><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>180</b></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu126.jpg" alt="Image ml156fu126.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu127.jpg" alt="Image ml156fu127.jpg" /></div></td><td headers="hd_h_ml156.t7_1_1_1_1 hd_h_ml156.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.35</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t8"><div id="ml156.t8" class="table"><h3><span class="label">Table 8</span><span class="title">Analogs with modification at the 2 position of the quinazoline core</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t8_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t8_1_1_1_1" colspan="4" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu128.jpg" alt="Image ml156fu128.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t8_1_1_1_1" id="hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound number</th><th headers="hd_h_ml156.t8_1_1_1_1" id="hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t8_1_1_1_1" id="hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml156.t8_1_1_1_1" id="hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N370S<br />AC<sub>50</sub> (μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>181</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK56229/bin/ml156fu129.jpg" alt="Image ml156fu129.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">H</td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.58</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>103</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu130.jpg" alt="Image ml156fu130.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu131.jpg" alt="Image ml156fu131.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.32</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>182</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu132.jpg" alt="Image ml156fu132.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu133.jpg" alt="Image ml156fu133.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>183</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu134.jpg" alt="Image ml156fu134.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu135.jpg" alt="Image ml156fu135.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>184</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu136.jpg" alt="Image ml156fu136.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu137.jpg" alt="Image ml156fu137.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>185</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu138.jpg" alt="Image ml156fu138.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu139.jpg" alt="Image ml156fu139.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">79.97</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>186</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu140.jpg" alt="Image ml156fu140.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu141.jpg" alt="Image ml156fu141.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.00</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>187</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu142.jpg" alt="Image ml156fu142.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu143.jpg" alt="Image ml156fu143.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>188</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu144.jpg" alt="Image ml156fu144.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu145.jpg" alt="Image ml156fu145.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.27</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>189</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu146.jpg" alt="Image ml156fu146.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu147.jpg" alt="Image ml156fu147.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.09</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>190</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu148.jpg" alt="Image ml156fu148.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu149.jpg" alt="Image ml156fu149.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.29</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>191</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu150.jpg" alt="Image ml156fu150.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu151.jpg" alt="Image ml156fu151.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">200.86</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>192</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu152.jpg" alt="Image ml156fu152.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu153.jpg" alt="Image ml156fu153.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>193</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu154.jpg" alt="Image ml156fu154.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu155.jpg" alt="Image ml156fu155.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>194</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu156.jpg" alt="Image ml156fu156.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu157.jpg" alt="Image ml156fu157.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>195</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu158.jpg" alt="Image ml156fu158.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu159.jpg" alt="Image ml156fu159.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>196</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu160.jpg" alt="Image ml156fu160.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu161.jpg" alt="Image ml156fu161.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40.09</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>197</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu162.jpg" alt="Image ml156fu162.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu163.jpg" alt="Image ml156fu163.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.67</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>198</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu164.jpg" alt="Image ml156fu164.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu165.jpg" alt="Image ml156fu165.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>199</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu166.jpg" alt="Image ml156fu166.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu167.jpg" alt="Image ml156fu167.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>200</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu168.jpg" alt="Image ml156fu168.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu169.jpg" alt="Image ml156fu169.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>201</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu170.jpg" alt="Image ml156fu170.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu171.jpg" alt="Image ml156fu171.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15.95</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>202</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu172.jpg" alt="Image ml156fu172.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu173.jpg" alt="Image ml156fu173.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">100.67</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>203</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu174.jpg" alt="Image ml156fu174.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu175.jpg" alt="Image ml156fu175.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>204</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu176.jpg" alt="Image ml156fu176.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu177.jpg" alt="Image ml156fu177.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>205</b></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu178.jpg" alt="Image ml156fu178.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu179.jpg" alt="Image ml156fu179.jpg" /></div></td><td headers="hd_h_ml156.t8_1_1_1_1 hd_h_ml156.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40.09</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t9"><div id="ml156.t9" class="table"><h3><span class="label">Table 9</span><span class="title">Analogs with modifications at the molecular core</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t9/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t9_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t9_1_1_1_1" colspan="5" rowspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu180.jpg" alt="Image ml156fu180.jpg" /></div></th></tr><tr><th headers="hd_h_ml156.t9_1_1_1_1" id="hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound number</th><th headers="hd_h_ml156.t9_1_1_1_1" id="hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Molecular core</th><th headers="hd_h_ml156.t9_1_1_1_1" id="hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml156.t9_1_1_1_1" id="hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml156.t9_1_1_1_1" id="hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">N370S<br />AC50 (μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>103</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu181.jpg" alt="Image ml156fu181.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu182.jpg" alt="Image ml156fu182.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu183.jpg" alt="Image ml156fu183.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.32</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>206</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu184.jpg" alt="Image ml156fu184.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu185.jpg" alt="Image ml156fu185.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu186.jpg" alt="Image ml156fu186.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>207</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu187.jpg" alt="Image ml156fu187.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu188.jpg" alt="Image ml156fu188.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu189.jpg" alt="Image ml156fu189.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20.08</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>208</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu190.jpg" alt="Image ml156fu190.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu191.jpg" alt="Image ml156fu191.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu192.jpg" alt="Image ml156fu192.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.00</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>209</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu193.jpg" alt="Image ml156fu193.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu194.jpg" alt="Image ml156fu194.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu195.jpg" alt="Image ml156fu195.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>210</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu196.jpg" alt="Image ml156fu196.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu197.jpg" alt="Image ml156fu197.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu198.jpg" alt="Image ml156fu198.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10.31</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>211</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu199.jpg" alt="Image ml156fu199.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu200.jpg" alt="Image ml156fu200.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu201.jpg" alt="Image ml156fu201.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>212</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu202.jpg" alt="Image ml156fu202.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu203.jpg" alt="Image ml156fu203.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu204.jpg" alt="Image ml156fu204.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.18</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>213</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu205.jpg" alt="Image ml156fu205.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu206.jpg" alt="Image ml156fu206.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu207.jpg" alt="Image ml156fu207.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>214</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu208.jpg" alt="Image ml156fu208.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu209.jpg" alt="Image ml156fu209.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu210.jpg" alt="Image ml156fu210.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>215</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu211.jpg" alt="Image ml156fu211.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu212.jpg" alt="Image ml156fu212.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu213.jpg" alt="Image ml156fu213.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>216</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu214.jpg" alt="Image ml156fu214.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu215.jpg" alt="Image ml156fu215.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu216.jpg" alt="Image ml156fu216.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>217</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu217.jpg" alt="Image ml156fu217.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu218.jpg" alt="Image ml156fu218.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu219.jpg" alt="Image ml156fu219.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>218</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu220.jpg" alt="Image ml156fu220.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu221.jpg" alt="Image ml156fu221.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu222.jpg" alt="Image ml156fu222.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>219</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu223.jpg" alt="Image ml156fu223.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu224.jpg" alt="Image ml156fu224.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu225.jpg" alt="Image ml156fu225.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>220</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu226.jpg" alt="Image ml156fu226.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu227.jpg" alt="Image ml156fu227.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu228.jpg" alt="Image ml156fu228.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>221</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu229.jpg" alt="Image ml156fu229.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu230.jpg" alt="Image ml156fu230.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu231.jpg" alt="Image ml156fu231.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr><tr><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>222</b></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu232.jpg" alt="Image ml156fu232.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu233.jpg" alt="Image ml156fu233.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK56229/bin/ml156fu234.jpg" alt="Image ml156fu234.jpg" /></div></td><td headers="hd_h_ml156.t9_1_1_1_1 hd_h_ml156.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Inactive</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml156f2"><div id="ml156.f2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f2.jpg" alt="Figure 2. Chaperone activity of ML156/CID 9893924/NCGC00159568 and others using wildtype and homozygous, mutant N370S GC fibroblasts." /></div><h3><span class="label">Figure 2</span><span class="title">Chaperone activity of <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924/NCGC00159568 and others using wildtype and homozygous, mutant N370S GC fibroblasts</span></h3><div class="caption"><p>Two genotypes of fibroblasts, fibroblasts homozygous for wildtype GC (top) and fibroblasts homozygous for N370S GC (bottom) were stained both with a Cy3-labeled antibody for GC protein content (first row) and a FITC-labeled antibody specific for lysosomal compartments (LAMP1; second row) after treatment with (1) DMSO vehicle, (2) 10 μM Isofagomine, (3) 10μM NCGC00182292, and (4) 1μM <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924/NCGC00159568. Isofagomine, NCGC00182292 and <a href="/pcsubstance/?term=ML156[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML156</a>/CID 9893924/NCGC00159568 show increased lysosomal GC protein after treatment.</p></div></div></article><article data-type="table-wrap" id="figobml156t10"><div id="ml156.t10" class="table"><h3><span class="label">Table 10</span><span class="title">Mouse microsomal stability assay at 60 minutes</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t10/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t10_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Plus NADPH</th><th id="hd_h_ml156.t10_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Minus NADPH</th><th id="hd_h_ml156.t10_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th id="hd_h_ml156.t10_1_1_1_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th></tr><tr><th headers="hd_h_ml156.t10_1_1_1_1" id="hd_h_ml156.t10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_2" id="hd_h_ml156.t10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_3" id="hd_h_ml156.t10_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_4" id="hd_h_ml156.t10_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Parent remaining</th><th headers="hd_h_ml156.t10_1_1_1_5" id="hd_h_ml156.t10_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_6" id="hd_h_ml156.t10_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_7" id="hd_h_ml156.t10_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Parent remaining</th><th headers="hd_h_ml156.t10_1_1_1_8" id="hd_h_ml156.t10_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th><th headers="hd_h_ml156.t10_1_1_1_9" id="hd_h_ml156.t10_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></th></tr><tr><th headers="hd_h_ml156.t10_1_1_1_1 hd_h_ml156.t10_1_1_2_1 hd_h_ml156.t10_1_1_3_1" id="hd_h_ml156.t10_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml156.t10_1_1_1_2 hd_h_ml156.t10_1_1_2_2 hd_h_ml156.t10_1_1_3_2" id="hd_h_ml156.t10_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">test species</th><th headers="hd_h_ml156.t10_1_1_1_3 hd_h_ml156.t10_1_1_2_3" id="hd_h_ml156.t10_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">test conc</th><th headers="hd_h_ml156.t10_1_1_1_4 hd_h_ml156.t10_1_1_2_4" id="hd_h_ml156.t10_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<sup>st</sup></th><th headers="hd_h_ml156.t10_1_1_1_5 hd_h_ml156.t10_1_1_2_5" id="hd_h_ml156.t10_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2<sup>nd</sup></th><th headers="hd_h_ml156.t10_1_1_1_6 hd_h_ml156.t10_1_1_2_6" id="hd_h_ml156.t10_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">mean</th><th headers="hd_h_ml156.t10_1_1_1_7 hd_h_ml156.t10_1_1_2_7" id="hd_h_ml156.t10_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1<sup>st</sup></th><th headers="hd_h_ml156.t10_1_1_1_8 hd_h_ml156.t10_1_1_2_8" id="hd_h_ml156.t10_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2<sup>nd</sup></th><th headers="hd_h_ml156.t10_1_1_1_9 hd_h_ml156.t10_1_1_2_9" id="hd_h_ml156.t10_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">mean</th></tr><tr><th headers="hd_h_ml156.t10_1_1_1_3 hd_h_ml156.t10_1_1_2_3 hd_h_ml156.t10_1_1_3_3" id="hd_h_ml156.t10_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(uM)</th><th headers="hd_h_ml156.t10_1_1_1_4 hd_h_ml156.t10_1_1_2_4 hd_h_ml156.t10_1_1_3_4" id="hd_h_ml156.t10_1_1_4_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th><th headers="hd_h_ml156.t10_1_1_1_5 hd_h_ml156.t10_1_1_2_5 hd_h_ml156.t10_1_1_3_5" id="hd_h_ml156.t10_1_1_4_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th><th headers="hd_h_ml156.t10_1_1_1_6 hd_h_ml156.t10_1_1_2_6 hd_h_ml156.t10_1_1_3_6" id="hd_h_ml156.t10_1_1_4_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th><th headers="hd_h_ml156.t10_1_1_1_7 hd_h_ml156.t10_1_1_2_7 hd_h_ml156.t10_1_1_3_7" id="hd_h_ml156.t10_1_1_4_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th><th headers="hd_h_ml156.t10_1_1_1_8 hd_h_ml156.t10_1_1_2_8 hd_h_ml156.t10_1_1_3_8" id="hd_h_ml156.t10_1_1_4_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th><th headers="hd_h_ml156.t10_1_1_1_9 hd_h_ml156.t10_1_1_2_9 hd_h_ml156.t10_1_1_3_9" id="hd_h_ml156.t10_1_1_4_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">(%)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t10_1_1_1_1 hd_h_ml156.t10_1_1_2_1 hd_h_ml156.t10_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9893924</td><td headers="hd_h_ml156.t10_1_1_1_2 hd_h_ml156.t10_1_1_2_2 hd_h_ml156.t10_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">mouse</td><td headers="hd_h_ml156.t10_1_1_1_3 hd_h_ml156.t10_1_1_2_3 hd_h_ml156.t10_1_1_3_3 hd_h_ml156.t10_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td><td headers="hd_h_ml156.t10_1_1_1_4 hd_h_ml156.t10_1_1_2_4 hd_h_ml156.t10_1_1_3_4 hd_h_ml156.t10_1_1_4_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">59%</td><td headers="hd_h_ml156.t10_1_1_1_5 hd_h_ml156.t10_1_1_2_5 hd_h_ml156.t10_1_1_3_5 hd_h_ml156.t10_1_1_4_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57%</td><td headers="hd_h_ml156.t10_1_1_1_6 hd_h_ml156.t10_1_1_2_6 hd_h_ml156.t10_1_1_3_6 hd_h_ml156.t10_1_1_4_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">58%</td><td headers="hd_h_ml156.t10_1_1_1_7 hd_h_ml156.t10_1_1_2_7 hd_h_ml156.t10_1_1_3_7 hd_h_ml156.t10_1_1_4_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">99%</td><td headers="hd_h_ml156.t10_1_1_1_8 hd_h_ml156.t10_1_1_2_8 hd_h_ml156.t10_1_1_3_8 hd_h_ml156.t10_1_1_4_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">105%</td><td headers="hd_h_ml156.t10_1_1_1_9 hd_h_ml156.t10_1_1_2_9 hd_h_ml156.t10_1_1_3_9 hd_h_ml156.t10_1_1_4_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">102%</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml156t11"><div id="ml156.t11" class="table"><h3><span class="label">Table 11</span><span class="title">Concentrations of CID9893924 in plasma, brain, liver and tail; intraperitoneal administration twice at a 12 hour interval of CID9893924 at 20mg/kg dose in male Swiss Albino Mice (mean and SD)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t11/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t11_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;"></th><th id="hd_h_ml156.t11_1_1_1_2" colspan="8" rowspan="1" style="text-align:center;vertical-align:bottom;">CID9893924 Concentration (Mean ± SD)</th></tr><tr><th headers="hd_h_ml156.t11_1_1_1_1" id="hd_h_ml156.t11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;"></th><th headers="hd_h_ml156.t11_1_1_1_2" id="hd_h_ml156.t11_1_1_2_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:bottom;">Plasma</th><th headers="hd_h_ml156.t11_1_1_1_2" id="hd_h_ml156.t11_1_1_2_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:bottom;">Brain</th><th headers="hd_h_ml156.t11_1_1_1_2" id="hd_h_ml156.t11_1_1_2_4" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Liver</th><th headers="hd_h_ml156.t11_1_1_1_2" id="hd_h_ml156.t11_1_1_2_5" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Tail</th></tr><tr><th headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1" id="hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Time (h)</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2" id="hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">ng/mL</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2" id="hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">μM</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3" id="hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">ng/g</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3" id="hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">μM</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4" id="hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">ng/g</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4" id="hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">μMol/kg</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5" id="hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">ng/g</th><th headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5" id="hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">μM</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.083</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">7550.45±4133.97</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">13.57</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">156.27±35.04</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.28</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">114450.60±35495.51</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">205.72</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2382.09±1219.43</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4.28</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.25</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3718.63±1820.04</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">6.68</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">117.00±26.91</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.21</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">120015.98±31928.46</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">215.72</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1711.93±646.62</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3.08</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.5</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.39±0.68</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">144.25±59.45</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.26</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">172131.23±63886.67</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">309.39</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2757.54±1415.49</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4.96</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2027.95±1490.37</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3.65</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">249.35±85.99</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.45</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">188379.50±53862.08</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">338.6</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4515.56±419.31</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">8.12</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2782.05±2546.66</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">264.68±62.48</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.48</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">197983.68±86771.35</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">355.86</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3948.02±857.57</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">7.1</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3433.14±323.70</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">6.17</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">334.73±9.89</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.6</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">274815.45±33548.02</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">493.96</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4607.28±480.57</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">8.28</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">8</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3058.29±852.34</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5.5</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">263.30±75.11</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.47</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">161336.35±97210.11</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">289.99</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4237.98±474.45</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">7.62</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">12</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">68.72±21.67</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.12</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">25.60±27.39</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.05</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3178.62±487.48</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5.71</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1635.27±1112.20</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2.94</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">13</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4356.09±262.37</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">7.83</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">65.50±29.60</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.12</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">96094.83±50368.63</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">172.72</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3048.19±974.44</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5.48</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">15</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1332.21±889.37</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2.39</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">114.42±18.10</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.21</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">121269.48±27551.90</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">217.97</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4746.46±442.57</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">8.53</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">17</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.00±0.00</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.00±0.00</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.00±0.00</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">72.02±47.26</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.13</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">20</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1242.59±477.67</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2.23</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">78.98±24.56</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.14</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">101618.15±16886.07</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">182.65</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3217.71±2165.76</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5.78</td></tr><tr><td headers="hd_h_ml156.t11_1_1_1_1 hd_h_ml156.t11_1_1_2_1 hd_h_ml156.t11_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">24</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">171.61±126.71</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_2 hd_h_ml156.t11_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.31</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">39.90±23.35</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_3 hd_h_ml156.t11_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">0.07</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">8024.95±6437.87</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_4 hd_h_ml156.t11_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">14.42</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">3230.88±1784.48</td><td headers="hd_h_ml156.t11_1_1_1_2 hd_h_ml156.t11_1_1_2_5 hd_h_ml156.t11_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">5.81</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml156f3"><div id="ml156.f3" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK56229/bin/ml156f3.jpg" alt="Figure 3. Structure-activity relationship (SAR) study for CID 9893924 (8i)." /></div><h3><span class="label">Figure 3</span><span class="title">Structure-activity relationship (SAR) study for CID 9893924 (<b>8i</b>)</span></h3></div></article><article data-type="table-wrap" id="figobml156t12"><div id="ml156.t12" class="table"><h3><span class="label">Table 12</span><span class="title">Comparison of GC inhibitory activities with Somatostatin receptor sst4 activity</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK56229/table/ml156.t12/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml156.t12_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Entry</th><th id="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NCGC ID</th><th id="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cmpd. No</th><th id="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th id="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th id="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">GC AC50 (nM)</th><th id="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">sst4 Ki (nM)</th></tr></thead><tbody><tr><td headers="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td><td headers="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00159568-03</td><td headers="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>8i</b></td><td headers="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9893924</td><td headers="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449177" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449177</a></td><td headers="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">600</td><td headers="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">17</td></tr><tr><td headers="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00185838-01</td><td headers="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>8g</b></td><td headers="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44820544</td><td headers="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449192" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449192</a></td><td headers="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">46000</td><td headers="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">690</td></tr><tr><td headers="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3</td><td headers="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187947-01</td><td headers="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>26</b></td><td headers="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44820569</td><td headers="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449202" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449202</a></td><td headers="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2800</td><td headers="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">19</td></tr><tr><td headers="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187948-01</td><td headers="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>24</b></td><td headers="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44820545</td><td headers="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449203" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449203</a></td><td headers="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1300</td><td headers="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">160</td></tr><tr><td headers="hd_h_ml156.t12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5</td><td headers="hd_h_ml156.t12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">NCGC00187949-01</td><td headers="hd_h_ml156.t12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>27</b></td><td headers="hd_h_ml156.t12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44820563</td><td headers="hd_h_ml156.t12_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/89449204" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">89449204</a></td><td headers="hd_h_ml156.t12_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18000</td><td headers="hd_h_ml156.t12_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">26</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><script type="text/javascript" src="/core/mathjax/2.7.9/MathJax.js?config=TeX-AMS-MML_SVG"> </script></div></div>
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