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<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK98917" /><meta name="ncbi_domain" content="mlprobe" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK98917/" /><meta name="ncbi_pagename" content="Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1) - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
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<title>Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1) - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Probe Reports from the NIH Molecular Libraries Program [Internet]" /><meta name="citation_title" content="Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1)" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2011/12/12" /><meta name="citation_author" content="Katsunori Tsuboi" /><meta name="citation_author" content="Daniel A Bachovchin" /><meta name="citation_author" content="Anna E Speers" /><meta name="citation_author" content="Steven J Brown" /><meta name="citation_author" content="Timothy Spicer" /><meta name="citation_author" content="Virneliz Fernandez-Vega" /><meta name="citation_author" content="Jill Ferguson" /><meta name="citation_author" content="Benjamin F Cravatt" /><meta name="citation_author" content="Peter Hodder" /><meta name="citation_author" content="Hugh Rosen" /><meta name="citation_pmid" content="22834034" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK98917/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1)" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Katsunori Tsuboi" /><meta name="DC.Contributor" content="Daniel A Bachovchin" /><meta name="DC.Contributor" content="Anna E Speers" /><meta name="DC.Contributor" content="Steven J Brown" /><meta name="DC.Contributor" content="Timothy Spicer" /><meta name="DC.Contributor" content="Virneliz Fernandez-Vega" /><meta name="DC.Contributor" content="Jill Ferguson" /><meta name="DC.Contributor" content="Benjamin F Cravatt" /><meta name="DC.Contributor" content="Peter Hodder" /><meta name="DC.Contributor" content="Hugh Rosen" /><meta name="DC.Date" content="2011/12/12" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK98917/" /><meta name="description" content="Glutathione transferases (GSTs) are a superfamily of enzymes that conjugate glutathione to a wide variety of both exogenous and endogenous compounds for biotransformation and/or removal. Using activity-based proteomic methods, glutathione S-tranferase omega (GSTO1) has been shown to be overexpressed in human cancer cell lines that show enhanced aggressiveness. Other studies have implicated GSTO1 in chemotherapeutic resistance. Cancer remains one of the most life-threatening diseases for which effective treatments and cures are lacking. Recently, targeted therapeutics (i.e., selective inhibitors that block individual enzymes) have shown great promise for the treatment of cancer. Inhibiting GSTO1 may thus offer a new therapeutic strategy for cancer. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a selective GSTO1 inhibitor probe, ML175, by high-throughput screening using fluorescence polarization-activity-based protein profiling (FluoPol-ABPP), and several rounds of gel-based competitive activity-based protein profiling (ABPP) secondary assays employing SAR analysis of selected compounds. ML175, a hindered alpha-chloroacetamide, was identified as a highly potent and selective inhibitor of the target enzyme GSTO1. ML175 has an IC50 of 28 nM, greater than 350-fold selectivity against potential anti-targets as assessed by competitive ABPP profiling, and has been shown to be active in situ, completely inhibiting GSTO1 at 250 nM compound concentration. As determined from LC-MS/MS analysis, ML175 is an activity-based inhibitor; it covalently labels the active site cysteine nucleophile of GSTO1. ML175 has favorable stability, solubility, and cytotoxicity profile, and improves on the current state of the art for GSTO1 inhibitors. Taken together, our findings suggest that it is very possible to develop potent and selective probes based on tempered electrophilic scaffolds, and that ML175 will be a highly successful probe for biochemical investigation of GSTO1." /><meta name="og:title" content="Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1)" /><meta name="og:type" content="book" /><meta name="og:description" content="Glutathione transferases (GSTs) are a superfamily of enzymes that conjugate glutathione to a wide variety of both exogenous and endogenous compounds for biotransformation and/or removal. Using activity-based proteomic methods, glutathione S-tranferase omega (GSTO1) has been shown to be overexpressed in human cancer cell lines that show enhanced aggressiveness. Other studies have implicated GSTO1 in chemotherapeutic resistance. Cancer remains one of the most life-threatening diseases for which effective treatments and cures are lacking. Recently, targeted therapeutics (i.e., selective inhibitors that block individual enzymes) have shown great promise for the treatment of cancer. Inhibiting GSTO1 may thus offer a new therapeutic strategy for cancer. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a selective GSTO1 inhibitor probe, ML175, by high-throughput screening using fluorescence polarization-activity-based protein profiling (FluoPol-ABPP), and several rounds of gel-based competitive activity-based protein profiling (ABPP) secondary assays employing SAR analysis of selected compounds. ML175, a hindered alpha-chloroacetamide, was identified as a highly potent and selective inhibitor of the target enzyme GSTO1. ML175 has an IC50 of 28 nM, greater than 350-fold selectivity against potential anti-targets as assessed by competitive ABPP profiling, and has been shown to be active in situ, completely inhibiting GSTO1 at 250 nM compound concentration. As determined from LC-MS/MS analysis, ML175 is an activity-based inhibitor; it covalently labels the active site cysteine nucleophile of GSTO1. ML175 has favorable stability, solubility, and cytotoxicity profile, and improves on the current state of the art for GSTO1 inhibitors. Taken together, our findings suggest that it is very possible to develop potent and selective probes based on tempered electrophilic scaffolds, and that ML175 will be a highly successful probe for biochemical investigation of GSTO1." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK98917/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/mlprobe/ml175/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK98917/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/core/mathjax/2.7.9/MathJax.js?config=/corehtml/pmc/js/mathjax-config-classic.3.4.js"></script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/mlprobe/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" alt="Cover of Probe Reports from the NIH Molecular Libraries Program" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Probe Reports from the NIH Molecular Libraries Program [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK98917_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK98917_dtls__"><div>Bethesda (MD): National Center for Biotechnology Information (US); 2010-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/mlprobe/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml176/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml174/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK98917_"><span class="title" itemprop="name">Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase
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Omega 1 (GSTO1)</span></h1><p class="contrib-group"><span itemprop="author">Katsunori Tsuboi</span>, <span itemprop="author">Daniel A Bachovchin</span>, <span itemprop="author">Anna E Speers</span>, <span itemprop="author">Steven J Brown</span>, <span itemprop="author">Timothy Spicer</span>, <span itemprop="author">Virneliz Fernandez-Vega</span>, <span itemprop="author">Jill Ferguson</span>, <span itemprop="author">Benjamin F Cravatt</span>, <span itemprop="author">Peter Hodder</span>, and <span itemprop="author">Hugh Rosen</span>.</p><a data-jig="ncbitoggler" href="#__NBK98917_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK98917_ai__"><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Katsunori Tsuboi</span>,<sup>*</sup> <span itemprop="author">Daniel A Bachovchin</span>,<sup>*</sup> <span itemprop="author">Anna E Speers</span>,<sup>*</sup> <span itemprop="author">Steven J Brown</span>,<sup>*</sup> <span itemprop="author">Timothy Spicer</span>,<sup>†</sup> <span itemprop="author">Virneliz Fernandez-Vega</span>,<sup>†</sup> <span itemprop="author">Jill Ferguson</span>,<sup>*</sup> <span itemprop="author">Benjamin F Cravatt</span>,<sup>*</sup> <span itemprop="author">Peter Hodder</span>,<sup>†</sup> and <span itemprop="author">Hugh Rosen</span><sup>†</sup>.<sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup></p><h4>Affiliations</h4><div class="affiliation"><sup>*</sup>
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The Scripps Research Institute, La Jolla CA</div><div class="affiliation"><sup>†</sup>
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The Scripps Research Institute, Jupiter, FL</div><div class="affiliation"><sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup>Corresponding author:
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<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.sppircs@nesorh" class="oemail">ude.sppircs@nesorh</a></div></div><p class="small">Received: <span itemprop="datePublished">August 31, 2010</span>; Last Update: <span itemprop="dateModified">December 12, 2011</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p>Glutathione transferases (GSTs) are a superfamily of enzymes that conjugate
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glutathione to a wide variety of both exogenous and endogenous compounds for
|
||
biotransformation and/or removal. Using activity-based proteomic methods,
|
||
glutathione S-tranferase omega (GSTO1) has been shown to be overexpressed in human
|
||
cancer cell lines that show enhanced aggressiveness. Other studies have implicated
|
||
GSTO1 in chemotherapeutic resistance. Cancer remains one of the most
|
||
life-threatening diseases for which effective treatments and cures are lacking.
|
||
Recently, targeted therapeutics (i.e., selective inhibitors that block individual
|
||
enzymes) have shown great promise for the treatment of cancer. Inhibiting GSTO1 may
|
||
thus offer a new therapeutic strategy for cancer. The Scripps Research Institute
|
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Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe
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||
Production Centers Network (MLPCN), identified a selective GSTO1 inhibitor probe,
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||
<a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a>, by high-throughput screening using fluorescence
|
||
polarization-activity-based protein profiling (FluoPol-ABPP), and several rounds of
|
||
gel-based competitive activity-based protein profiling (ABPP) secondary assays
|
||
employing SAR analysis of selected compounds. <a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a>, a hindered
|
||
alpha-chloroacetamide, was identified as a highly potent and selective inhibitor of
|
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the target enzyme GSTO1. <a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a> has an IC<sub>50</sub> of 28 nM, greater
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than 350-fold selectivity against potential anti-targets as assessed by competitive
|
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ABPP profiling, and has been shown to be active in situ, completely inhibiting GSTO1
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at 250 nM compound concentration. As determined from LC-MS/MS analysis, <a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a> is an activity-based inhibitor; it covalently labels the
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||
active site cysteine nucleophile of GSTO1. <a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a> has favorable
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||
stability, solubility, and cytotoxicity profile, and improves on the current state
|
||
of the art for GSTO1 inhibitors. Taken together, our findings suggest that it is
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very possible to develop potent and selective probes based on tempered electrophilic
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scaffolds, and that <a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a> will be a highly successful probe for
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biochemical investigation of GSTO1.</p></div><div class="h2"></div><p>Assigned Assay Grant #: 1 R01 CA087660-05</p><p>Screening Center Name & PI: Scripps Research Institute Molecular Screening Center (SRIMSC), H. Rosen</p><p>Chemistry Center Name & PI: SRIMSC, H. Rosen</p><p>Assay Submitter & Institution: BF Cravatt, TSRI, La Jolla</p><p>PubChem Summary Bioassay Identifier (AID): <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2175" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2175</a></p><div id="ml175.s1"><h2 id="_ml175_s1_">Probe Structure & Characteristics</h2><div id="ml175.fu1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK98917/bin/ml175fu1.jpg" alt="ML175." /></div><h3><span class="title"><a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a></span></h3></div><div id="ml175.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK98917/table/ml175.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml175.tu1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ml175.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID/ML#</th><th id="hd_h_ml175.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target Name</th><th id="hd_h_ml175.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> (nM) [SID, AID]</th><th id="hd_h_ml175.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti-target Name(s)</th><th id="hd_h_ml175.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> (μM) [SID, AID]<sup><a class="bk_pop" href="#ml175.tfn1">*</a></sup></th><th id="hd_h_ml175.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Fold Selective<sup><a class="bk_pop" href="#ml175.tfn2">†</a></sup></th><th id="hd_h_ml175.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary Assay(s) (nM) [SID, Name: IC<sub>50</sub> AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml175.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 4257368/<a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a></td><td headers="hd_h_ml175.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">GSTO1</td><td headers="hd_h_ml175.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">28 [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463081</a>]</td><td headers="hd_h_ml175.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>30 thiol-based enzymes</td><td headers="hd_h_ml175.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>10 [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>]</td><td headers="hd_h_ml175.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>350</td><td headers="hd_h_ml175.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>LC-MS/MS assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449772" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449772</a>]<br /><b>Cytox assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449773" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449773</a>]<br /><b>Gel-based ABPP:</b> IC<sub>50</sub>: 28 nM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463081</a>]<br /><b>Cell-based assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463094</a>]<br /><b>Endogenous enzyme assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709100" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709100</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463098" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463098</a>]<br /><b>Click chem assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463101</a>]<br /><b>Selectivity assay:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>]<br /><b>Gel-based ABPP:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709100" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709100</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>*</dt><dd><div id="ml175.tfn1"><p class="no_margin">IC<sub>50</sub> of the anti-target is defined as greater than the test compound concentration at which less than or equal to 50% inhibition of the anti-target is observed, which is reported in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>. For <a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>, no anti-targets were observed at 10 μM in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>, so the IC<sub>50</sub> is reported as > 10 μM.</p></div></dd><dt>†</dt><dd><div id="ml175.tfn2"><p class="no_margin">Fold-selectivity was calculated as: > IC50 for anti-target/IC50 for target</p></div></dd></dl></div></div></div></div><div id="ml175.s2"><h2 id="_ml175_s2_">Recommendations for scientific use of the probe</h2><p>The probe target, glutathione S-tranferase omega (GSTO1), is overexpressed in several human cancer cell lines that show enhanced aggressiveness [<a class="bk_pop" href="#ml175.r1">1</a>], and has been implicated in chemotherapeutic resistance [<a class="bk_pop" href="#ml175.r2">2</a>]. Nonetheless, no studies to date have characterized GSTO1’s function in cancer by pharmacological inhibition of the enzyme, due to a lack of selective inhibitors. As such, the probe described in this report will aid in primary research investigations into GSTO1 involvement in the dysregulated biochemical pathways that support tumorigenesis. Because GSTO1 has already been identified as highly expressed in several cancer cell lines, including MDA-MB-231 and MDA-MB-435 [<a class="bk_pop" href="#ml175.r3">3</a>], excellent model systems are available to assess the role of GSTO1 in supporting tumorigenesis, including chemotoxic resistance, proliferation, and invasion. Because GSTO1 has been proposed to play an important role in chemoresistance in cancer cells, this probe may serve as a lead for drug development efforts aimed at inhibiting GSTO1. Currently there exists no suitable inhibitor of GSTO1 for these primary research studies or for analysis as a potential therapeutic agent. We previously identified a modestly potent 120 nM inhibitor [<a class="bk_pop" href="#ml175.r4">4</a>], and a 51 nM inhibitor has also been recently reported [<a class="bk_pop" href="#ml175.r5">5</a>]; however the latter compound undergoes hydrolysis by endogenous esterases, rendering the compound cell-impermeable. The probe compound described in this report is the most potent GSTO1 inhibitor described to date and does not suffer from a susceptibility to enzymatic hydrolysis. As such, this probe provides a necessary alternative for both <i>in vitro</i> and <i>in situ</i> studies, and may potentially serve as a prototype for therapeutic intervention.</p></div><div id="ml175.s3"><h2 id="_ml175_s3_">1. Introduction</h2><p>Glutathione transferases (GSTs) are a superfamily of enzymes that conjugate glutathione to a wide variety of both exogenous and endogenous compounds for biotransformation and/or removal [<a class="bk_pop" href="#ml175.r6">6</a>]. Using activity-based proteomic methods, we discovered that glutathione S-tranferase omega (GSTO1) is overexpressed in human cancer cell lines that show enhanced aggressiveness [<a class="bk_pop" href="#ml175.r1">1</a>], and other studies have implicated GSTO1 in chemotherapeutic resistance [<a class="bk_pop" href="#ml175.r2">2</a>]. Cancer remains one of the most life-threatening diseases for which effective treatments and cures are lacking. Historically, cancer has been treated with general chemotoxic agents; however, because these agents essentially kill all cells at a rate proportional to their proliferation, general chemotoxins offer only a modest therapeutic window. Recently, targeted therapeutics (i.e., selective inhibitors that block individual enzymes) have shown great promise for the treatment of cancer. Inhibiting GSTO1 may thus offer a new therapeutic strategy for cancer. Development of a selective inhibitor would also aid in primary research investigations into GSTO1 involvement in the dysregulated biochemical pathways that support tumorigenesis. GSTO1 is highly expressed in several cancer cell lines, including MDA-MB-231 and MDA-MB-435 [<a class="bk_pop" href="#ml175.r3">3</a>], offering an ideal model for <i>in vitro</i> and <i>in situ</i> studies of the role of GSTO1 in supporting tumorigeneisis, possibly through detoxification of chemotherapeutic reagents [<a class="bk_pop" href="#ml175.r2">2</a>].</p><p>GSTO1 has a catalytic cysteine residue and is consequently sensitive to broadly reactive thiol alkylating agents, including N-ethylmaleimide [<a class="bk_pop" href="#ml175.r7">7</a>]. A limited number of substrate assays have been developed, but these are not well-suited for HTS due to poor turnover rates and/or reliance on UV absorbance at short wavelengths (305 nm), where many small-molecules exhibit intrinsic absorbance [<a class="bk_pop" href="#ml175.r8">8</a>]. GSTO1 is, however, highly reactive with sulfonate ester (SE) [<a class="bk_pop" href="#ml175.r3">3</a>] and chloroacetamide (CA) [<a class="bk_pop" href="#ml175.r9">9</a>] activity-based protein profiling (ABPP) probes. This reactivity can be exploited for inhibitor discovery using a competitive-ABPP platform [<a class="bk_pop" href="#ml175.r10">10</a>], whereby small molecule enzyme inhibition is assessed by the ability to out-compete ABPP probe labeling of the target enzyme. When used in the context of a complex proteome, competitive-ABPP also offers a means to assess inhibitor selectivity against a wide range of probe-reactive enzymes. Competitive-ABPP has been configured to operate in a high-throughput manner via fluorescence polarization readout, FluoPol-ABPP [<a class="bk_pop" href="#ml175.r4">4</a>]. As such, inhibitor discovery by FluoPol–ABPP offers a unique opportunity to develop inhibitors for this important enzyme. Previously, we used a small FluoPol-ABPP HTS screen of the Maybridge HitFinder Library to identify an alpha chloroacetamide compound capable of inhibiting GSTO1 with an IC<sub>50</sub> of 120 nM (compound <b>66</b>, <a class="figpopup" href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" rid-figpopup="figml175f7" rid-ob="figobml175f7">Figure 7</a>) [<a class="bk_pop" href="#ml175.r4">4</a>]. However, compound <b>66</b>, did not readily lend itself to SAR manipulation to improve potency. This preliminary result did, however, suggest that tempered alpha-chloroacetamide electrophiles may offer a window for selective inhibition of GSTO1. We thus initiated a FluoPol HTS assay at the Scripps Research Institute Molecule Screening Center (SRIMSC) to uncover more potent lead scaffolds. Shortly following completion of this HTS assay, Son <i>et al.</i> [<a class="bk_pop" href="#ml175.r5">5</a>] reported that the commercially available fluorescent protein tag, CellTracker Green (5-chloromethylfluorescein diacetate, Invitrogen, <a class="figpopup" href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" rid-figpopup="figml175f7" rid-ob="figobml175f7">Figure 7</a>), was a potent and selective inhibitor of GSTO1 with an IC<sub>50</sub> of 51 nM. While this probe may be useful for certain applications, it readily undergoes hydrolysis by endogenous esterases, rendering the compound membrane-impermeable. The probe described in this report does not have the same metabolic susceptibility as the CellTracker reagent, and is almost twice as potent (IC<sub>50</sub> 28 nM).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f7" co-legend-rid="figlgndml175f7"><a href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" title="Figure 7" class="img_link icnblk_img figpopup" rid-figpopup="figml175f7" rid-ob="figobml175f7"><img class="small-thumb" src="/books/NBK98917/bin/ml175f7.gif" src-large="/books/NBK98917/bin/ml175f7.jpg" alt="Figure 7. Prior Art GSTO1 Inhibitors." /></a><div class="icnblk_cntnt" id="figlgndml175f7"><h4 id="ml175.f7"><a href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" rid-ob="figobml175f7">Figure 7</a></h4><p class="float-caption no_bottom_margin">Prior Art GSTO1 Inhibitors. </p></div></div></div><div id="ml175.s4"><h2 id="_ml175_s4_">2. Materials and Methods</h2><p>Solubility, stability, and glutathione reactivity analyses were conducted in accordance with NIH guidelines. All reagents for chemical synthesis were obtained from ThermoFisher or SigmaAldrich. NMR characterization was done using 300mHz Bruker instrumentation. All other protocols are reported in the AIDs summarized below.</p><div id="ml175.s5"><h3>2.1. Assays</h3><div id="ml175.s6"><h4>Primary uHTS assay to identify GSTO1 inhibitors (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1974" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1974</a>)</h4><p><b>Assay Overview</b>: The purpose of this assay was to identify compounds that act as inhibitors of GSTO1. This assay also served as a counterscreen to identify thiol-reactive compounds identified as active in a set of previous experiments entitled, “Primary biochemical high throughput screening assay to identify inhibitors of Retinoblastoma binding protein 9 (RBBP9)” (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1515" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1515</a>). Recombinant GSTO1 protein was incubated with test compounds and a rhodamine (Rh)-conjugated sulfonate ester (SE) activity-based probe. The reaction was excited with linear polarized light and the intensity of the emitted light was measured as the polarization value (mP). As designed, test compounds that act as GSTO1 inhibitors will prevent GSTO1-probe interactions, thereby increasing the proportion of free (unbound) fluorescent probe in the well, leading to low fluorescence polarization. Compounds were tested in singlicate at a final nominal concentration of 5.96 micromolar.</p><p><b>Protocol Summary</b>: Prior to the start of the assay, 4.0 μL of Assay Buffer (0.01% Pluronic detergent, 50 mM Tris HCl pH 8.0, 150 mM NaCl, 1 mM DTT) containing GSTO1 (1.25 μM) was dispensed into 1536-well microtiter plates. Next, test compound (30 nL in DMSO) or DMSO alone (0.59% final concentration) was added to the appropriate wells and incubated for 30 minutes at 25 degrees Celsius. The assay was started by dispensing SE-Rh probe (1.0 μL of 375 nM in Assay Buffer) to all wells. Plates were centrifuged and incubated for 20 hours at 37 degrees Celsius. Prior to reading, plates were equilibrated at room temperature for 10 minutes. Fluorescence polarization was read for 30 seconds for each polarization plane (parallel and perpendicular) on a Viewlux microplate reader (PerkinElmer, Turku, Finland) using a BODIPY TMR FP filter set and a BODIPY dichroic mirror (excitation = 525 nm, emission = 598 nm). The well fluorescence polarization value (mP) was obtained via the PerkinElmer Viewlux software.</p><p><b>Assay cutoff</b>: Compounds that inhibited GSTO1 greater than 34.81% were considered active.</p></div><div id="ml175.s7"><h4>Confirmation uHTS assay to identify GSTO1 inhibitors (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2176" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2176</a>)</h4><p><b>Assay Overview</b>: The purpose of this assay was to confirm activity of compounds identified as active in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1974" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1974</a>. Recombinant GSTO1 protein was incubated with test compounds and SE-Rh activity-based probe. The reaction was excited with linear polarized light and the intensity of the emitted light was measured as the polarization value (mP). As designed, test compounds that act as GSTO1 inhibitors will prevent GSTO1-probe interactions, thereby increasing the proportion of free (unbound) fluorescent probe in the well, leading to low fluorescence polarization. Compounds were tested in triplicate at a final nominal concentration of 5.96 micromolar.</p><p><b>Protocol Summary</b>: Prior to the start of the assay, 4.0 μL Assay Buffer (0.01% Pluronic detergent, 50 mM Tris HCl pH 8.0, 150 mM NaCl, 1 mM DTT) containing GSTO1 (1.25 μM) was dispensed into 1536-well microtiter plates. Next, test compound (30 nL in DMSO) or DMSO alone (0.59% final concentration) was added to the appropriate wells and incubated for 30 minutes at 25 degrees Celsius. The assay was started by dispensing SE-Rh probe (1.0 μL of 375 nM in Assay Buffer) to all wells. Plates were centrifuged and incubated for 20 hours at 37 degrees Celsius. Prior to reading, plates were equilibrated at room temperature for 10 minutes. Plates were analyzed as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1974" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1974</a>). <b>Assay cutoff</b>: Compounds that inhibited GSTO1 greater than 34.81% were considered active.</p></div><div id="ml175.s8"><h4>Inhibition of recombinant GSTO1 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine whether or not test compounds identified by HTS can inhibit recombinant GSTO1. In this gel-based competitive-ABPP assay, recombinant GSTO1 was incubated with test compound followed by reaction with a rhodamine-conjugated sulfonate ester (SE-Rh) activity-based probe. The reaction products were separated by SDS-PAGE and visualized in-gel using a flatbed fluorescence scanner. The percentage activity remaining was determined by measuring the integrated optical density (IOD) of the bands. As designed, test compounds that act as GSTO1 inhibitors will prevent GSTO1-probe interactions, thereby decreasing the proportion of bound fluorescent probe, giving lower fluorescence intensity in the band in the gel. Percent inhibition was calculated relative to a DMSO (no compound) control.</p><p><b>Protocol Summary:</b> Recombinant GSTO1 (250 nM in 50 μL of DPBS) was incubated with 1 μM test compound (1 μL of a 50x stock in DMSO) for 30 minutes at 25 degrees Celsius followed by reaction with 10 μM SE-Rh (1 μL of 50x stock in DMSO) for 1 hour at 25 degrees Celsius. The reaction was quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 band relative to a DMSO-only (no compound) control. <b>Assay cutoff:</b> Compounds that inhibited GSTO1 at least 75% were considered active.</p></div><div id="ml175.s9"><h4>Inhibition of endogenous GSTO1: 1 μM compound (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463098" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463098</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine whether test compounds can inhibit endogenous GSTO1 in the presence of complex proteomic lysate. In this gel-based competitive ABPP assay, MDA-MB-435 soluble proteome was incubated with test compound followed by reaction with SE-Rh and analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>).</p><p><b>Protocol Summary:</b> MDA-MB-435 soluble proteome (1 mg/mL in DPBS) was incubated with 1 μM test compound (1 μL of a 50x stock in DMSO) for 30 minutes at 25 degrees Celsius. The proteome was then labeled with 10 μM SE-Rh (1 μL of a 50x stock in DMSO) for 1 hour at 25 degrees Celsius. The reaction was quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 band relative to a DMSO-only (no compound) control. <b>Assay cutoff:</b> Compounds that inhibited GSTO1 at least 90% were considered active.</p></div><div id="ml175.s10"><h4>Inhibition of endogenous GSTO1: 10 μM, 1 μM, 0.1 μM compound potency and selectivity analysis (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine whether test compounds can inhibit endogenous GSTO1 in a complex proteomic lysate and to assess the extent of their anti-target reactivity. In this gel-based competitive-ABPP assay, MDA-MB-435 soluble proteome was incubated with test compound followed by reaction with a SE-Rh or rhodamine-conjugated alpha-chloroacetamide (CA-Rh) activity-based probe. The reaction products were analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>).</p><p><b>Protocol Summary:</b> MDA-MB-435 soluble proteome (1 mg/mL in DPBS) was incubated with 0.1, 1, or 10 μM test compound (1 μL of a 50x stock in DMSO) for 30 minutes at 25 degrees Celsius. The proteome was then labeled with 10 μM SE-Rh (1 μL of a 50x stock in DMSO) or 5 μM CA-Rh (1 μL of a 50x stock in DMSO) for 1 hour at 25 degrees Celsius. The reaction was quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 or anti-target band relative to a DMSO-only (no compound) control. Anti-target bands at 70 kDa, 55 kDa, 52 kDa, 49 kDa, 38 kDa, 34 kDa, 32 kDa, and 15 kDa were assessed. <b>Assay cutoff:</b> Compounds that inhibited GSTO1 at least 80% at 0.1 micromolar with no anti-targets were considered active.</p></div><div id="ml175.s11"><h4>Inhibition of endogenous GSTO1 <i>in situ</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463094</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine whether or not test compounds can inhibit GSTO1 <i>in situ</i>. In this gel-based competitive-ABPP assay, cultured MDA-MB-435 cells were incubated with test compound. Cells were harvested and the soluble fraction was isolated and reacted with a rhodamine-conjugated sulfonate ester (SE-Rh) activity-based probe. The reaction products were analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>).</p><p><b>Protocol Summary:</b> MDA-MB-435 cells in media (5 mL total volume; supplemented with FCS) were treated with 1 μM test compound (5 μL of a 1000x stock in DMSO) for 1 hour at 37 degrees Celsius. Cells were harvested, washed 4 times with 10 mL DPBS, and homogenized by sonication in DPBS. The soluble fraction was isolated by centrifugation (100K × g, 45 minutes) and the protein concentration was adjusted to 1 mg/mL with DPBS. SE-Rh (1 μL of 50x stock in DMSO) was added to a final concentration of 10 μM in 50 μL total reaction volume. The reaction was incubated for 1 hour at 25 degrees Celsius, quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 band relative to a DMSO-only (no compound) control. <b>Assay cutoff</b>: Compounds that inhibited GSTO1 at least 90% were considered active.</p></div><div id="ml175.s12"><h4>Comparison of competitive ABPP and CC-ABPP <i>In Vitro</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463101</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to compare inhibition of GSTO1 by an inhibitor compound in a competitive ABPP assay (<b>Assay 1</b>) to inhibition by the same compound in a direct ABPP assay using click chemistry (CC) (<b>Assay 2</b>). In <b>Assay 1</b>, MDA-MB-435 soluble proteome was incubated with test compound and then reacted with SE-Rh activity-based probe. In <b>Assay 2</b>, labeling of GSTO1 in proteome aliquots was assessed directly (rather than by competition) by appending an azide-conjugated rhodamine tag (Rh-N3) by CC to the alkyne analog test compounds. For both assays, the reaction products were analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>). For <b>Assay 1</b>, test compounds that act as GSTO1 inhibitors will prevent GSTO1-probe interactions, thereby decreasing the proportion of bound fluorescent probe, giving lower fluorescence intensity in the GSTO1 band in the gel. For <b>Assay 2</b>, the percent labeling was determined by measuring the IOD of the GSTO1 relative to the highest test concentration; compounds that act as GSTO1 inhibitors will bind GSTO1, and, following conjugation with the rhodamine tag, will cause an increase in the fluorescence intensity in the GSTO1 band in the gel.</p><p><b>Protocol Summary:</b> MDA-MB-435 soluble proteome (1 mg/mL in DPBS) was treated with 1 μM, 250 nM, 63 nM or 16 nM test compound (1 μL of 50x stock in DMSO) for 30 minutes at 25 degrees Celsius. For <b>Assay 1</b>, SE-Rh (1 μL of 50x stock in DMSO) was added to a final concentration of 10 μM in 50 μL total reaction volume. For <b>Assay 2</b>, separate proteome sample aliquots were reacted with Rh-N3 (50 μM) under click chemistry reaction conditions (1 mM TCEP, 100 μM TBTA ligand, 1 mM Cu(II)sulfate). Compound <a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a> was not tested in Assay 2 because Assay 2 is not applicable to non-alkyne compounds. <b>For both assays</b>, after addition of reagents, the reaction was incubated for 1hour at 25 degrees Celsius, quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning.</p><p>For <b>Assay 1</b>, the percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 band relative to a DMSO-only (no compound) control. <b>Assay cutoff:</b> Compounds with at least 80% inhibition at 63 nanomolar were considered active.</p><p>For <b>Assay 2</b>, the IOD of the GSTO1 band for the lower concentrations (250 nM, 63 nM and 16 nM) was calculated relative to IOD of GSTO1 for the highest concentration (1 μM) of test compound. <b>Assay cutoff:</b> A GSTO1 signal of at least 80% at 63 nanomolar as compared to 1 micromolar was considered active.</p></div><div id="ml175.s13"><h4>Comparison of competitive ABPP and CC-ABPP <i>In Situ</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463093" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463093</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to compare inhibition of GSTO1 by an inhibitor compound in a competitive ABPP assay (<b>Assay 1</b>) compared to inhibition by the same compound in a direct ABPP assay using CC (<b>Assay 2</b>). In <b>Assay 1</b>, cultured MDA-MB-435 cells were incubated with test compound. Cells were harvested and the soluble fraction was isolated and reacted with SE-Rh. In <b>Assay 2</b>, labeling of GSTO1 in proteome aliquots was assessed directly (rather than by competition) by appending Rh-N3 by click chemistry. For both assays, the reaction products were analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>) For <b>Assay 1</b>, test compounds that act as GSTO1 inhibitors will prevent GSTO1-probe interactions, thereby decreasing the proportion of bound fluorescent probe, giving lower fluorescence intensity in the GSTO1 band in the gel. For <b>Assay 2</b>, compounds that act as GSTO1 inhibitors will bind GSTO1, and following conjugation with the rhodamine tag, will cause an increase in the fluorescence intensity in the GSTO1 band in the gel.</p><p><b>Protocol Summary:</b> MDA-MB-435 cells in media (5 mL total volume; supplemented with FCS) were treated with 1 μM, 0.5 μM, and 0.25 μM test compound (1 μL of 1000x stock [1 mM, 500 μM, or 250 μM, respectively] in DMSO) for 1 hour at 37 degrees Celsius. Cells were harvested, washed 4 times with 10 mL DPBS, and homogenized by sonication in DPBS. The soluble fraction was isolated by centrifugation (100K × g, 45 minutes) and the protein concentration was adjusted to 1 mg/mL with DPBS. For <b>Assay 1</b>, SE-Rh (1 μL of 50x stock in DMSO) was added to a final concentration of 10 μM in 50 μL total reaction volume. For <b>Assay 2</b>, separate proteome sample aliquots were reacted with Rh-N3 (50 μM) under CC reaction conditions (1 mM TCEP, 100 μM TBTA ligand, 1 mM Cu(II)sulfate). <b>For both assays</b>, after addition of reagents, the reaction was incubated for 1 hour at 25 degrees Celsius, quenched with 2x SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning.</p><p>For <b>Assay 1</b>, the percentage activity remaining was determined by measuring the integrated optical density of the GSTO1 band relative to a DMSO-only (no compound) control. <b>Assay cutoff:</b> Compounds that inhibited GSTO1 at least 90% were considered active.</p><p>For <b>Assay 2</b>, the IOD of the GSTO1 band was calculated relative to background. <b>Assay cutoff:</b> A GSTO1 signal of at least 5-fold above background was considered active.</p></div><div id="ml175.s14"><h4>Determination of IC<sub>50</sub> values (AIDs <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463081</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463142</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine the IC50 values for powder samples of synthesized compounds. In this gel-based competitive-ABPP assay, SE-Rh was used to label GSTO1 in the presence of test compounds. The reaction products were analyzed by gel as described above (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>).</p><p><b>Protocol Summary:</b> Recombinant GSTO1 (250 nM) in assay buffer (DPBS with 0.01% pluronic detergent) was incubated with DMSO or compound for 30 minutes at 25 degrees Celsius before the addition of PS-Rh at a final concentration of 10 μM in 50 μL total reaction volume. The reaction was incubated for 1 hour at 25 degrees Celsius, quenched with 2X SDS-PAGE loading buffer, separated by SDS-PAGE and visualized by in-gel fluorescent scanning. The percentage activity remaining was determined by measuring the integrated optical density of the bands. IC<sub>50</sub> values for inhibition of GSTO1 were determined from dose-response curves from three trials at each inhibitor concentration (7-point series from 3 μM to 3 nM). <b>Assay cutoff</b>: Compounds with an IC<sub>50</sub> value of less than 1 μM were considered active.</p></div><div id="ml175.s15"><h4>Analysis of Cytotoxicity (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449773" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449773</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine cytotoxicity of inhibitor compounds belonging to the alpha-chloroacetamide scaffold. In this assay, MDA-MB-435 cells in either serum-free media (<b>Assay 1</b>) or serum-supplemented media (<b>Assay 2</b>) were incubated with test compounds, followed by determination of cell viability. The assay utilizes the CellTiter-Glo luminescent reagent to measure intracellular ATP in viable cells. Luciferase present in the reagent catalyzes the oxidation of beetle luciferin to oxyluciferin and light in the presence of cellular ATP. Well luminescence is directly proportional to ATP levels and cell viability. As designed, compounds that reduce cell viability will reduce ATP levels, luciferin oxidation and light production, resulting in decreased well luminescence. Compounds were tested in quadruplicate in a 7-point 1:10 dilution series starting at a nominal test concentration of 125 μM.</p><p><b>Protocol Summary:</b> This assay was started by dispensing MDA-MB-435 cells in RPMI media (15 μL, 8 × 10<sup>3</sup> cells/well) into a 384-well plate. Both serum-free media (<b>Assay 1</b>) and media supplemented with fetal calf serum (FCS) (<b>Assay 2</b>) were tested. Compound (5 μL of 0–500 μM in media containing 5% DMSO) was added to each well, giving final compound concentrations of 0–125 μM. Cells were incubated for 48 hours at 37 degrees Celsius in a humidified incubator and cell viability was determined by the CellTitre-Glo assay (Promega) according to manufacturer instructions. <b>Assay cutoff</b>: Compounds with a CC<sub>50</sub> value of less than 10 μM were considered active (cytotoxic).</p></div><div id="ml175.s16"><h4>LC-MS/MS Analysis of Inhibitor Binding Mode (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449772" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449772</a>)</h4><p><b>Assay Overview:</b> The purpose of this assay was to assess the binding mode of inhibitor compounds belonging to the alpha chloroacetamide scaffold and determine whether or not they covalently label the active site cysteine of GSTO1. In this assay, purified enzyme was reacted with inhibitor compounds, digested with trypsin, and the resulting peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The resulting data were analyzed to identify sites of covalent labeling.</p><p><b>Protocol Summary:</b> Four aliquots (25 μL) of GSTO1 (50 μM in DPBS) were prepared. Three inhibitor compounds (1 μL of 250 mM in DMSO) were added to three separate aliquots, giving a final concentration of 10 μM. To the fourth (control) aliquot was added DMSO (1 μL). Reactions were gently vortexed and incubated at 25 degrees Celsius for 30 minutes. To each reaction was added solid urea (25 mg), followed by freshly prepared aqueous ammonium bicarbonate (5 μL of 250 mM), and Millipore water to bring to total volume to 50 μL, giving final concentrations of 8 M urea and 25 mM ammonium bicarbonate. The reactions were vortexed until the urea was dissolved. To each reaction was added freshly prepared DTT (0.5 μL of 1 M in water, 10 mM [final]), and the reactions were incubated at 65 degrees Celsius for 15 minutes. To each reaction was then added freshly prepared IAA (4 μL of 0.5 mM in water, giving 20 mM [final]), and the reactions were incubated for 30 minutes at room temperature in the dark. Aqueous ammonium bicarbonate (140 μL of 25 mM) was added to reduce the urea concentration to 2 M. To each reaction was added sequencing grade modified trypsin (1 μg), and reactions were incubated at 37 degrees Celsius for 4 hours. The digests were acidified with formic acid (10 μL, giving 5% [final]). An Agilent 1200 series quaternary HPLC pump/autosampler system and Thermo Scientific Orbitrap Velos mass spectrometer were used for sample analysis. A fraction (15 μL) of the protein digest for each sample was autosampler-loaded onto a 100 micron fused-silica column (with a 5 micron in-house pulled tip) packed with 12 cm of Aqua C18 reversed-phase packing material. Chromatography was carried out using an increasing gradient of aqueous acetonitrile containing 0.1% formic acid over 125 minutes. Mass spectra were acquired in a data-dependent mode with dynamic exclusion and charge state screening (rejection of unassigned and +1 charge states) enabled.</p><p>The MS/MS spectra generated for each run were searched against a human protein database concatenated to a reversed decoy database using Sequest. For cysteine, both a static modification of +57.021 (for IAA alkylation) and variable modifications to account for possible inhibitor labeling (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205794" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205794</a>: 310.148; <a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205792" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205792</a>: 355.134; <a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>: 274.057) were specified. The resulting peptide identifications were assembled into protein identifications using DTASelect, and filters were adjusted to maintain a false discovery rate (as determined by number of hits against the reversed database) of <1%. Any modified peptides identified in the DMSO-treated sample were discarded as spurious hits. <b>Assay cutoff</b>: Compounds observed to modify the GSTO1 active site cysteine were considered active.</p></div></div><div id="ml175.s17"><h3>2.2. Probe Chemical Characterization</h3><div id="ml175.fu2" class="figure bk_fig"><div class="graphic"><img src="/books/NBK98917/bin/ml175fu2.jpg" alt="CID 4257368 SID 99205797 ML175." /></div><h3><span class="title">CID 4257368<br /><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a><br /><a href="/pcsubstance/?term=ML175[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML175</a></span></h3></div><p>The probe structure was verified by NMR (see <a href="#ml175.s18">section 2.3</a>) and high resolution MS (<i>m/z</i> calculated for C<sub>13</sub>H<sub>13</sub>ClF<sub>3</sub>N<sub>3</sub>O<sub>4</sub> [M+H]<sup>+</sup>: 368.0619; found: 368.0631), and purity was assessed to be greater than 95% by NMR. Liquid chromatography tandem mass spectrometry (LC-MS/MS) also gave the expected mass shift for the covalent probe-peptide adduct.</p><p>Solubility in PBS (137 mM NaCl, 2.7 mM KCl, 10 mM sodium phosphate dibasic, 2 mM potassium phosphate monobasic, pH 7.4) at room temperature was determined to be 480 μM, and the probe has a half-life of greater than 48 hours in PBS at room temperature (tested at 10 μM concentration, see <a class="figpopup" href="/books/NBK98917/figure/ml175.f1/?report=objectonly" target="object" rid-figpopup="figml175f1" rid-ob="figobml175f1">Figure 1</a>, below).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f1" co-legend-rid="figlgndml175f1"><a href="/books/NBK98917/figure/ml175.f1/?report=objectonly" target="object" title="Figure 1" class="img_link icnblk_img figpopup" rid-figpopup="figml175f1" rid-ob="figobml175f1"><img class="small-thumb" src="/books/NBK98917/bin/ml175f1.gif" src-large="/books/NBK98917/bin/ml175f1.jpg" alt="Figure 1. Stability of Compound 1 (NO3, SID 99205797) in PBS indicates a half-life of >48 hours." /></a><div class="icnblk_cntnt" id="figlgndml175f1"><h4 id="ml175.f1"><a href="/books/NBK98917/figure/ml175.f1/?report=objectonly" target="object" rid-ob="figobml175f1">Figure 1</a></h4><p class="float-caption no_bottom_margin">Stability of Compound 1 (NO3, SID 99205797) in PBS indicates a half-life of >48 hours. </p></div></div><p>The following compounds have been submitted to the SMR collection:</p><div id="ml175.t1" class="table"><h3><span class="label">Table 1</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/NBK98917/table/ml175.t1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml175.t1_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Designation</th><th id="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound Number</th><th id="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound Lab Name</th><th id="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SRID</th><th id="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th id="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th id="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th></tr></thead><tbody><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Probe</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>1</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">N03</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000764868-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 4257368</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126529</td></tr><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Analog 1</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>21</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">G10</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000699776-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 4380267</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205794" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205794</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126531</td></tr><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Analog 2</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>27</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">E09</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000703338-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 12004949</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205792" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205792</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126530</td></tr><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Analog 3</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>28</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">J04</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000703271-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 12004950</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205793</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126532</td></tr><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Analog 4</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>17</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A04-2</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000709884-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 4381127</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205796</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126533</td></tr><tr><td headers="hd_h_ml175.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>Analog 5</b></td><td headers="hd_h_ml175.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><b>25</b></td><td headers="hd_h_ml175.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">A03-2</td><td headers="hd_h_ml175.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SR-01000704049-3</td><td headers="hd_h_ml175.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID 4381126</td><td headers="hd_h_ml175.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205795" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205795</a></td><td headers="hd_h_ml175.t1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS003126534</td></tr></tbody></table></div></div></div><div id="ml175.s18"><h3>2.3. Probe Preparation</h3><div id="ml175.fu3" class="figure"><div class="graphic"><img src="/books/NBK98917/bin/ml175fu3.jpg" alt="Image ml175fu3" /></div></div><p>p-Fluoronitrobenzene (0.50 g, 3.5 mmol) was treated with 1,3-diaminopropane (2.6 mL, 35 mmol, 10 eq) and the reaction mixture was stirred at 100 degrees Celsius for 30 minutes. The reaction mixture was cooled to room temperature and treated with H<sub>2</sub>O (30 mL). After the mixture was stirred for 1 hour, the resulting precipitate was filtered and dried by vacuum to provide <b>A</b> (0.60 g, 89%) as a yellow crystalline solid.</p><p><sup>1</sup>H NMR (CDCl<sub>3</sub>, 300 MHz) δ 8.21-7.96 (m, 2H), 6.59-6.43 (m, 2H), 5.74 (s, 1H), 3.38-3.24 (m, 2H), 2.92 (t, <i>J</i> = 6.2 Hz, 2H), 1.88-1.70 (m, 2H). Purity >95% as estimated by NMR.</p><div id="ml175.fu4" class="figure"><div class="graphic"><img src="/books/NBK98917/bin/ml175fu4.jpg" alt="Image ml175fu4" /></div></div><p>A solution of <b>A</b> (0.50 g, 2.6 mmol) in CH<sub>2</sub>Cl<sub>2</sub> (20 mL) was treated with trifluoroacetic anhydride (0.91 mL, 6.5 mmol, 2.5 eq) and K<sub>2</sub>CO<sub>3</sub> (1.8 g, 13 mmol, 5.0 eq), and the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into H<sub>2</sub>O and extracted with CH<sub>2</sub>Cl<sub>2</sub> (x2). The organic layer was dried (Na<sub>2</sub>SO<sub>4</sub>) and concentrated under reduced pressure. The residue was re-dissolved in MeOH (20 mL), and K<sub>2</sub>CO<sub>3</sub> (1.8 g, 13 mmol, 5.0 eq) was added to the mixture. The reaction mixture was stirred for 30 minutes at room temperature. Water was added to the mixture and the MeOH evaporated under reduced pressure. The resulting aqueous solution was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous NaCl, dried (Na<sub>2</sub>SO<sub>4</sub>), and concentrated under reduced pressure. Chromatography (SiO<sub>2</sub>, 30 g, 50% ethyl acetate-hexane) afforded <b>B</b> (0.56 g, 75%) as a yellow solid.</p><p><sup>1</sup>H NMR (CDCl<sub>3</sub>, 300 MHz) δ 8.14-8.00 (m, 2H), 6.79-6.44 (m, 3H), 4.95 (m, 1H), 3.52 (q, <i>J</i> = 6.5 Hz, 2H), 3.31 (q, <i>J</i> = 6.5 Hz, 2H), 1.92 (quin, <i>J</i> = 6.5 Hz, 2H). Purity >95% as estimated by NMR.</p><div id="ml175.fu5" class="figure"><div class="graphic"><img src="/books/NBK98917/bin/ml175fu5.jpg" alt="Image ml175fu5" /></div></div><p>A solution of <b>B</b> (0.33 g, 1.13 mmol) in toluene (5 mL) was treated with chloroacetyl chloride (0.18 mL, 2.26 mmol, 2.0 eq), and the reaction mixture was stirred for 30 min at 100 degrees Celsius. The reaction mixture was poured into saturated aqueous Na<sub>2</sub>CO<sub>3</sub> and extracted with ethyl acetate. The organic layer was washed with H<sub>2</sub>O and saturated aqueous NaCl, dried (Na<sub>2</sub>SO<sub>4</sub>) and concentrated under reduced pressure. Chromatography (SiO<sub>2</sub>, 30 g, 33–50% ethyl acetate-hexane) afforded compound <b>1</b> (0.37 g, 89%) as a yellow solid.</p><p><sup>1</sup>H NMR (CDCl<sub>3</sub>, 300 MHz) δ 8.45-8.32 (m, 2H), 7.65 (s, 1H), 7.53-7.43 (m, 2H), 3.87 (t, <i>J</i> = 6.3 Hz, 2H), 3.83 (s, 2H), 3.44 (q, <i>J</i> = 6.3 Hz, 2H), 1.77 (quin, <i>J =</i> 6.3 Hz, 2H). Purity >95% as estimated by NMR. HRMS: <i>m/z</i> calculated for C<sub>13</sub>H<sub>13</sub>ClF<sub>3</sub>N<sub>3</sub>O<sub>4</sub> [M+H]<sup>+</sup>: 368.0619; found: 368.0631.</p></div></div><div id="ml175.s19"><h2 id="_ml175_s19_">3. Results</h2><p>Compound <b>1</b> (see <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a>) satisfies the following goals established at the inception of the project : 1) probes should be selective for GSTO1 among the reactive thiol-containing enzymes in human cell line proteomes as assessed by gel-based competitive activity-based protein profiling (ABPP), and 2) probes should exhibit an IC<sub>50</sub> of <10 μM and preferably <1 μM. An IC<sub>50</sub> value of 28 nM was derived from gel-based competitive ABPP data (<b>see <a href="#ml175.s21">Section 3.2</a>)</b>. A search of more than 30 ABPP probe-reactive anti-target enzymes yielded data for target/anti-target selectivity. Among this group of anti-targets, compound <b>1</b> has no activity at 10 μM, indicating that anti-target IC<sub>50</sub>s were all above 10 μM. Compound <b>1</b> was additionally shown to inhibit GSTO1 more than 90% in live cells.</p><div id="ml175.s20"><h3>3.1. Summary of Screening Results</h3><p>In the primary uHTS assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1974" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1974</a>), ~302K compounds were screened by FluoPol-ABPP with the SE-Rh probe using fluorescence polarization readout. A total of 3207 compounds (1.1%) were active, passing the set threshold of 34.81% GSTO1 inhibition. In the confirmation uHTS screen (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2176" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2176</a>), 2,374 active compounds were retested in triplicate, and 1,286 compounds (54%) were confirmed as active (<a class="figpopup" href="/books/NBK98917/figure/ml175.f2/?report=objectonly" target="object" rid-figpopup="figml175f2" rid-ob="figobml175f2">Figure 2</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f2" co-legend-rid="figlgndml175f2"><a href="/books/NBK98917/figure/ml175.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml175f2" rid-ob="figobml175f2"><img class="small-thumb" src="/books/NBK98917/bin/ml175f2.gif" src-large="/books/NBK98917/bin/ml175f2.jpg" alt="Figure 2. Flow chart describing uHTS screening results." /></a><div class="icnblk_cntnt" id="figlgndml175f2"><h4 id="ml175.f2"><a href="/books/NBK98917/figure/ml175.f2/?report=objectonly" target="object" rid-ob="figobml175f2">Figure 2</a></h4><p class="float-caption no_bottom_margin">Flow chart describing uHTS screening results. </p></div></div><p>Initially, 126 active compounds were ordered as liquids from DPI for secondary screening: 33 epoxides, 30 aryl chlorides, and 63 hindered alpha-chloroacetamides (i.e., bearing tertiary nitrogens). The first assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>) assessed whether or not test compounds could inhibit recombinant GSTO1 at 1 μM compound concentration using a gel-based competitive ABPP assay with the SE-Rh activity-based probe (see <a class="figpopup" href="/books/NBK98917/figure/ml175.f8/?report=objectonly" target="object" rid-figpopup="figml175f8" rid-ob="figobml175f8">Supplemental Figure S1</a>). A threshold cutoff of 75% inhibition was set for compounds to be considered active. A total of 37 compounds (1 epoxide, 10 aryl-chlorides, and 26 hindered alpha-chloroacetamides) passed the screening criteria.</p><p>The next gel-based competitive-ABPP secondary assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463098" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463098</a>) was designed to assess whether or not compounds could inhibit endogenous GSTO1 in the context of a complex proteome at 1 μM concentration. In addition to the 37 compounds that passed the first screening criteria, 21 compounds close to the threshold and 24 new compounds ordered from DPI (all hindered alpha-chloroacetamides) were screened (see <a class="figpopup" href="/books/NBK98917/figure/ml175.f9/?report=objectonly" target="object" rid-figpopup="figml175f9" rid-ob="figobml175f9">Supplemental Figure S2</a>). Of the combined 82 compounds, 22 compounds (2 epoxides, 3 aryl-chlorides, and 17 hindered alpha-chloroacetamides) passed the 90% inhibition threshold.</p><p>The second round of gel-based competitive-ABPP secondary screening (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>) involved assessment of potency at a lower (0.1 μM) concentration in the complex proteome and an assessment of anti-target selectivity at a higher (10 μM) concentration in the complex proteome using both the SE-Rh and CA-Rh activity-based probes (See <a class="figpopup" href="/books/NBK98917/figure/ml175.f10/?report=objectonly" target="object" rid-figpopup="figml175f10" rid-ob="figobml175f10">Supplemental Figure S3</a>). Because the two probes have different target enzymes, we were able to expand the search for anti-targets (more than 30 ABPP probe-reactive enzymes) outside the standard profile of SE-Rh by using both probes. Anti-targets were scored as hits and included in <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a> if they were inhibited by more than 50% for a given test compound concentration. A total of 22 compounds (all had passed the second round of screening) were tested in both of these assays. A total of 6 compounds (all hindered alpha-chloroacetamides) passed the 80% inhibition threshold at 0.1 μM, and 5 compounds (2 epoxides, 1 aryl-chloride, and 2 hindered alpha-chloroacetamides) passed the requirement for no observed off-targets at 10 μM. Only two compounds, the alpha-chloroacetamides <b>1</b> and <b>28</b>, passed both filters.</p><p>A final round of gel-based competitive-ABPP secondary screening (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463094</a>) aimed to determine whether or not compounds could inhibit GSTO1 <i>in situ</i> at 1 μM concentration (See <a class="figpopup" href="/books/NBK98917/figure/ml175.f11/?report=objectonly" target="object" rid-figpopup="figml175f11" rid-ob="figobml175f11">Supplemental Figure S4</a>). In addition to the 2 compounds that passed round three, 12 additional compounds were tested in this assay. Of the 14 total compounds tested, 6 compounds (all hindered alpha-chloroacetamides, including <b>1</b>) passed the 90% inhibition threshold, indicating that they could successfully inhibit GSTO1 in live cells. Thus, of the original 126 compounds subjected to secondary screening, only compound <b>1</b> was shown to inhibit GSTO1 potently and selectivity <i>in vitro</i>, and to have strong inhibitory activity against GSTO1 in live cells. Its IC<sub>50</sub> value was subsequently determined to be 28 nM.</p></div><div id="ml175.s21"><h3>3.2. Dose Response Curves for Probe</h3><p>IC<sub>50</sub> values were obtained from gel-based competitive ABPP data (<a class="figpopup" href="/books/NBK98917/figure/ml175.f3/?report=objectonly" target="object" rid-figpopup="figml175f3" rid-ob="figobml175f3">Figure 3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f3" co-legend-rid="figlgndml175f3"><a href="/books/NBK98917/figure/ml175.f3/?report=objectonly" target="object" title="Figure 3" class="img_link icnblk_img figpopup" rid-figpopup="figml175f3" rid-ob="figobml175f3"><img class="small-thumb" src="/books/NBK98917/bin/ml175f3.gif" src-large="/books/NBK98917/bin/ml175f3.jpg" alt="Figure 3. Dose response curve used to generate IC50 for probe compound." /></a><div class="icnblk_cntnt" id="figlgndml175f3"><h4 id="ml175.f3"><a href="/books/NBK98917/figure/ml175.f3/?report=objectonly" target="object" rid-ob="figobml175f3">Figure 3</a></h4><p class="float-caption no_bottom_margin">Dose response curve used to generate IC<sub>50</sub> for probe compound. </p></div></div></div><div id="ml175.s22"><h3>3.3. Scaffold/Moiety Chemical Liabilities</h3><p>The parameters of the uHTS assay were designed specifically to identify irreversible (rather than reversible) inhibitors of GSTO1. During secondary screening, we focused on the following electrophilic subtypes: epoxides, aryl-chlorides, and alpha-chloroacetamides. The alpha-chloroacetamide scaffold clearly emerged as the most effective lead in terms of potency, selectivity, and <i>in situ</i> efficacy. The probe compound and two analogs have been shown to covalently modify the catalytic cysteine in the GSTO1 active site.</p><p>The probe compound showed no reactivity with glutathione (100 μM), indicating that it is not generally cysteine reactive, but rather has a tempered electrophilicity and specific structural elements that direct reactivity towards GSTO1.</p><p>An irreversible probe has some distinct advantages over reversible analogs. Targets can be readily characterized by methods such as mass spectrometry and click chemistry-ABPP, required dosing is often lower, irreversible compounds are not as sensitive to pharmacokinetic parameters, and administration can induce long-lasting inhibition [<a class="bk_pop" href="#ml175.r11">11</a>]. In the case of the EGFR inhibitor PD 0169414, its irreversibility and high selectivity were credited with producing prolonged inhibition of the target, alleviating concerns over short plasma half-lives and reducing the need for high peak plasma levels, thus minimizing potential nonspecific toxic effects [<a class="bk_pop" href="#ml175.r12">12</a>].</p><p>Indeed, over a third of enzymatic drug targets are irreversibly inhibited by currently marketed drugs [<a class="bk_pop" href="#ml175.r13">13</a>]. Examples of covalent enzyme-inhibitor pairs include serine type <span class="small-caps">d</span>-Ala-<span class="small-caps">d</span>-Ala carboxypeptidase, which is covalently modified by all beta-lactam antibiotics, acetylcholinesterase, whose active site serine undergoes covalent modification by pyridostigmine, prostaglandin-endoperoxide synthase, which is the target of the ubiquitously prescribed aspirin, aromatase, which is irreversibly modified by exemestane, monoamine oxidase, which is covalently modified by <span class="small-caps">l</span>-deprenyl, thymidylate synthase, which is covalently modified by floxuridine, H+/K+ ATPase, which undergoes covalent modification by omaprazole, esmoprazole, and lanoprazole, and triacylglycerol lipase, whose serine nucleophile is targeted by orlistat [<a class="bk_pop" href="#ml175.r13">13</a>].</p></div><div id="ml175.s23"><h3>3.4. SAR Tables</h3><p>As a whole, the N-phenyl alpha-chloroacetamide scaffold provided more potent compounds than the other two types of electrophilic scaffolds tested: the aryl chlorides (<b>111</b>–<b>140</b>) and epoxides (<b>141</b>–<b>173</b>). (Note: all compounds not included in <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a>, below, can be found in the <b>Supplemental SAR Tables [</b><a class="figpopup" href="/books/NBK98917/table/ml175.t4/?report=objectonly" target="object" rid-figpopup="figml175t4" rid-ob="figobml175t4">Tables S1</a>–<a class="figpopup" href="/books/NBK98917/table/ml175.t9/?report=objectonly" target="object" rid-figpopup="figml175t9" rid-ob="figobml175t9">S7</a><b>]</b>). The N-phenyl alpha-chloroacetamide subtype also proved to be the best variant among other alpha-chloroacetamide scaffolds in the uHTS screening library. Ring-constrained acetamides (<b>84</b>–<b>110</b>) produced no good leads, nor did scaffolds in which the phenyl was replaced with a non-aromatic substituent like dimethoxy ethane (e.g., compare <b>76</b>–<b>79</b> vs. <b>27</b>-<b>29</b>,<b>31</b>–<b>34</b>).There were also library examples of having the phenyl exchanged for a benzyl (<b>65</b>–<b>73</b>) or methyl-benzyl (<b>74</b>) with some activity retained provided that the nitrogen had a large substituent at <b>R2</b>/<b>R3</b> (i.e., compare <b>65</b>–<b>69</b> to <b>70</b>–<b>73</b>). A leading contender among the benzyl derivatives was compound <b>65</b>, a highly related analog of the previously identified 120 nM GSTO1 inhibitor, which was also in the uHTS screening library (compound <b>66</b>). While significantly more potent than <b>66</b>, compound <b>65</b> suffered from a high anti-target hit rate (having 2 anti-targets at 1μM and 7 anti-targets and 10 μM), and thus was discounted as a structural lead. There were also several examples of N-phenyl alpha-chloroacetamides in which R2/R3 formed a single, cyclic, substituent (<b>56</b>–<b>64</b>); however, none proved potent enough to pass secondary screening thresholds.</p><div id="ml175.t2" class="table"><h3><span class="label">Table 2</span><span class="title">SAR Analysis for Target</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml175.t2_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml175.t2_1_1_1_1" colspan="5" rowspan="2" headers="hd_h_ml175.t2_1_1_1_1" style="text-align:left;vertical-align:middle;"></th><th id="hd_h_ml175.t2_1_1_1_2" colspan="3" rowspan="2" headers="hd_h_ml175.t2_1_1_1_2" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu6.jpg" alt="Image ml175fu6.jpg" /></div></th><th id="hd_h_ml175.t2_1_1_1_3" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Potency and Selectivity Analysis<sup><a class="bk_pop" href="#ml175.tfn4">†</a></sup></th></tr><tr><th headers="hd_h_ml175.t2_1_1_1_3" id="hd_h_ml175.t2_1_1_2_1" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">% INH Endogenous GSTO1 <i>in vitro</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463110" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463110</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463102</a>)</th><th headers="hd_h_ml175.t2_1_1_1_3" id="hd_h_ml175.t2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">% INH GSTO1 <i>in situ</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463094</a>)</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" id="hd_h_ml175.t2_1_1_2_3" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">IC<sub>50</sub> (nM) (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463081</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463142</a>)</th><th headers="hd_h_ml175.t2_1_1_1_3" id="hd_h_ml175.t2_1_1_2_4" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Total anti-target hits (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>)<sup><a class="bk_pop" href="#ml175.tfn6">††</a></sup></th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" id="hd_h_ml175.t2_1_1_2_5" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">Target to anti-target fold selectivity<sup><a class="bk_pop" href="#ml175.tfn7">§</a></sup> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>)</th></tr><tr><th headers="hd_h_ml175.t2_1_1_1_1" id="hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Entry (lab name)</th><th headers="hd_h_ml175.t2_1_1_1_1" id="hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml175.t2_1_1_1_1" id="hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml175.t2_1_1_1_1" id="hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SRID</th><th headers="hd_h_ml175.t2_1_1_1_1" id="hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><sup><a class="bk_pop" href="#ml175.tfn3">*</a></sup></th><th headers="hd_h_ml175.t2_1_1_1_2" id="hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml175.t2_1_1_1_2" id="hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml175.t2_1_1_1_2" id="hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R3</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1" id="hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1 μM</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1" id="hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.1 μM</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2" id="hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1 μM</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4" id="hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1 μM</th><th headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4" id="hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 μM</th></tr></thead><tbody><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>1</b> (N03)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 4257368</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709100" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709100</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000764868-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu7.jpg" alt="Image ml175fu7.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT<sup><a class="bk_pop" href="#ml175.tfn5">‡</a></sup></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000764868-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">98%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">28</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>350</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>2</b> (KT8)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245323</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107578" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107578</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000380-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu8.jpg" alt="Image ml175fu8.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">62%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">16%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>3</b> (KT10)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245318</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107580" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107580</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000382-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu9.jpg" alt="Image ml175fu9.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">94%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">34%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;"><100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>4</b> (KT9)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245316</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107579" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107579</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000381-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu10.jpg" alt="Image ml175fu10.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">90%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">29%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;"><100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>5</b> (KT3)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245315</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107574" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107574</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000376-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu11.jpg" alt="Image ml175fu11.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">59%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">97%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>6</b> (KT14)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245319</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107583" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107583</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000385-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu12.jpg" alt="Image ml175fu12.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">23</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>430</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>7</b> (KT20)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829222</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205804" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205804</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000393-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu13.jpg" alt="Image ml175fu13.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">12</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>830</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8</b> (KT21)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829246</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205805" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205805</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000394-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu14.jpg" alt="Image ml175fu14.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">95%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">34</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>29</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>9</b> (KT1)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245322</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107572" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107572</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000374-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu15.jpg" alt="Image ml175fu15.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">51%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>10</b> (KT2)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245314</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107573" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107573</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000375-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-NO2</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu16.jpg" alt="Image ml175fu16.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">67%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>11</b> (KT19)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829223</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205803" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205803</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000392-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">90%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">40</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>250</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>12</b> (KT7)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829244</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205798" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205798</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000387-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-F</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">94%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">25%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>13</b> (KT17)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829245</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205801" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205801</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000390-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m-CF3</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">62%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>14</b> (KT15)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829237</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205799" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205799</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000388-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">90%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">27%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>15</b> (KT16)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829247</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205800" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205800</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000389-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Me</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">55%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">10%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>16</b> (KT18)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829248</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205802" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205802</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000391-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu17.jpg" alt="Image ml175fu17.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">73%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">16%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>17</b> (A04-2)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 4381127</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709057" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709057</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000709884-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
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||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205796" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205796</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000709884-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">38</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>26</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>18</b> (KT22)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829250</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205806" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205806</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000395-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">79%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>19</b> (KT25)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829238</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205809" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205809</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000398-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl, m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">96%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">45</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>22</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>20</b> (L08)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 4380266</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709063" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709063</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000711779-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">o-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT (40%) Rec<sup><a class="bk_pop" href="#ml175.tfn8">¶</a></sup></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>21</b> (G10)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 4380267</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709043" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709043</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000699776-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-F</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205794" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205794</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000699776-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">71%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">54</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>18</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>22</b> (KT11)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245320</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107581" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107581</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000383-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-F</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu19.jpg" alt="Image ml175fu19.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">48%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">95%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;"><100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>23</b> (KT23)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46829231</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205807" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205807</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000396-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-CF3</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">55%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">0%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;"><100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>24</b> (KT24)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 45107494</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205808" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205808</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000397-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m-CF3</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">92%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">28%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;"><100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>25</b> (A03-2)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 4381126</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709049" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709049</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000704049-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">97%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205795" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205795</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000704049-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">45%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">95%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">67</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>14</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>26</b> (J06)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 4381125</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709045" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709045</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703979-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Me, m-Me</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3-Pyridine</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">76%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>27</b> (E09)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 12004949</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709034" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709034</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703338-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205792" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205792</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703338-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">98%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">32</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>30</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>28</b> (J04)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">CID 12004950</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709042" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709042</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703271-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205793</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703271-3</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">91%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">60%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">22</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>450</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>29</b> (M04)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 12004770</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709050" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709050</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000704899-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">o-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT (28%) Rec<sup><a class="bk_pop" href="#ml175.tfn8">¶</a></sup></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>30</b> (F03-2)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 12004951</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709062" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709062</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000711529-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">62%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">87%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>31</b> (M09)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 4230741</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709058" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709058</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000709941-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Me</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu18.jpg" alt="Image ml175fu18.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">82%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>32</b> (KT5)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245313</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107576" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107576</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000378-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu19.jpg" alt="Image ml175fu19.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">83%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">90%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>33</b> (KT4)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245317</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107575" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107575</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000377-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu20.jpg" alt="Image ml175fu20.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">69%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">77%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>34</b> (KT6)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 46245321</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/96107577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 96107577</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000000379-1</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe-phenyl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu20.jpg" alt="Image ml175fu20.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">64%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">30%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">>100</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>35</b> (K03)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 3689413</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709052" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709052</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000705401-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-OMe, m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2-thiophene</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<div class="graphic"><img src="/books/NBK98917/bin/ml175fu21.jpg" alt="Image ml175fu21.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">100%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">88%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">95%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#99CC66;text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">>10</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>36</b> (H03-2)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 3689411</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709053" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709053</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000705537-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2-thiophene</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu21.jpg" alt="Image ml175fu21.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">88%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>37</b> (M08)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 3689416</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709046" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709046</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000703981-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">p-Ome</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2-thiophene</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu21.jpg" alt="Image ml175fu21.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">86%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr><tr><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>38</b> (F09)</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 3689415</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/92709047" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 92709047</a></td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000704041-2</td><td headers="hd_h_ml175.t2_1_1_1_1 hd_h_ml175.t2_1_1_3_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">P</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">m-Cl</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2-thiophene</td><td headers="hd_h_ml175.t2_1_1_1_2 hd_h_ml175.t2_1_1_3_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
||
<div class="graphic"><img src="/books/NBK98917/bin/ml175fu21.jpg" alt="Image ml175fu21.jpg" /></div></td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_9" rowspan="1" colspan="1" style="background-color:#FF9999;text-align:center;vertical-align:middle;">75%</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_1 hd_h_ml175.t2_1_1_3_10" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_2 hd_h_ml175.t2_1_1_3_11" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_3" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_12" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_4 hd_h_ml175.t2_1_1_3_13" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td><td headers="hd_h_ml175.t2_1_1_1_3 hd_h_ml175.t2_1_1_2_5" rowspan="1" colspan="1" style="background-color:#808080;text-align:center;vertical-align:middle;">NT</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>*</dt><dd><div id="ml175.tfn3"><p class="no_top_margin">P = Liquid sample from DPI; S = Synthesized</p></div></dd><dt>†</dt><dd><div id="ml175.tfn4"><p class="no_top_margin">Color scheme: green = passed threshold for activity; red = did not pass threshold for activity; grey = not tested</p></div></dd><dt>‡</dt><dd><div id="ml175.tfn5"><p class="no_top_margin">NT = Not Tested</p></div></dd><dt>††</dt><dd><div id="ml175.tfn6"><p class="no_top_margin">Anti-targets are reported as hits if >50% inhibition is observed at the given test compound concentration (1 or 10 μM) as reported in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a></p></div></dd><dt>§</dt><dd><div id="ml175.tfn7"><p class="no_top_margin">Fold-selectivity is reported as > Conc_≤50%_INH_Anti-target/Conc_>50%_INH_GSTO1 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>) where:
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<ul class="simple-list"><li class="half_rhythm"><div>Conc_≤50%_INH_Anti-target is the test compound concentration at which less than or equal to 50% inhibition of the anti-target is observed (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>), and</div></li><li class="half_rhythm"><div>Conc_>50%_INH_GSTO1 is the test compound concentration at which greater than 50% inhibition of GSTO1 is observed (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>)</div></li></ul></p><p>If the concentrations are both 1μM, fold selectivity is reported as <100 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>), except in cases where the target IC<sub>50</sub> has been determined, in which case fold-selectivity is reported as: > Conc_≤50%_INH_Anti-target/ IC<sub>50</sub>_Target, where:
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<ul class="simple-list"><li class="half_rhythm"><div>Conc_≤50%_INH_Anti-target is the test compound concentration at which less than or equal to 50% inhibition of the anti-target is observed (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>), and</div></li><li class="half_rhythm"><div>IC<sub>50</sub>_Target is the IC<sub>50</sub> against GSTO1 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463081</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463142</a>)</div></li></ul></p></div></dd><dt>¶</dt><dd><div id="ml175.tfn8"><p class="no_top_margin">Percent inhibition against recombinant GSTO1 is given (did not pass threshold for testing against endogenous GSTO1)</p></div></dd></dl></div></div></div><p>Starting with the N-phenyl alpha-chloroacetamide scaffold, we synthesized 23 related analogs, several of which have alkyne moieties for click chemistry (CC)-ABPP evaluation (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463101</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463093" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463093</a>). Also included in <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a> are 15 analogs obtained from DPI and 6 resynthesized compounds. The synthetic compounds were subject to analysis as outlined in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a> to determine potency and anti-target selectivity (See <a class="figpopup" href="/books/NBK98917/figure/ml175.f12/?report=objectonly" target="object" rid-figpopup="figml175f12" rid-ob="figobml175f12">Supplemental Figure S5</a>). Select compounds were also evaluated for <i>in situ</i> activity as outlined in <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463094" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463094</a> (<a class="figpopup" href="/books/NBK98917/figure/ml175.f11/?report=objectonly" target="object" rid-figpopup="figml175f11" rid-ob="figobml175f11">Supplemental Figure S4</a>). IC<sub>50</sub> values were determined for the probe, five analogs, and all synthetic compounds that exhibited greater than 90% inhibition of GSTO1 at 0.1 μM concentration (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463081" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AIDs 463081</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463142</a>).</p><p><i><u>SAR of R1</u>:</i> Listed in <a class="figpopup" href="/books/NBK98917/table/ml175.t3/?report=objectonly" target="object" rid-figpopup="figml175t3" rid-ob="figobml175t3">Table 3</a> are the relative potency rankings of <b>R1</b> as a function of the <b>R2</b> and <b>R3</b> substituents. While it is clear that there is a significant amount of inter-dependence between the left-(<b>R1</b>) and right- (<b>R2</b> and <b>R3</b>) hand sides of the molecule (e.g., relative order of p-fluoro and m-trifluoromethyl switch from A to B), specific overarching themes do emerge. In general the most potent <b>R1</b> groups are para-nitro, meta-chloro, and para-chloro. Compound <b>38</b> is somewhat of an anomaly; its low potency could be an anti-synergistic effect of the combined substituents or an analysis/compound error. Compared to meta or para substituents, ortho substituents are accompanied by a dramatic loss of activity. This steric intolerance for ortho substitution is also observed when <b>R2</b>=H and <b>R3</b>=hydroxyl quinolin (compounds <b>40</b>, <b>41</b> vs. <b>44</b>, <b>45</b>). Fused ring systems (i.e., having an <b>R1</b> substituent that transforms the phenyl to a napthalen) are similarly not tolerated (compound <b>48</b> vs. <b>39</b>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml175t3"><a href="/books/NBK98917/table/ml175.t3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml175t3" rid-ob="figobml175t3"><img class="small-thumb" src="/books/NBK98917/table/ml175.t3/?report=thumb" src-large="/books/NBK98917/table/ml175.t3/?report=previmg" alt="Table 3. SAR of R1." /></a><div class="icnblk_cntnt"><h4 id="ml175.t3"><a href="/books/NBK98917/table/ml175.t3/?report=objectonly" target="object" rid-ob="figobml175t3">Table 3</a></h4><p class="float-caption no_bottom_margin">SAR of R1. </p></div></div><p><i><u>SAR of R2</u>:</i> Several derivatives are tolerated at <b>R2</b>, including hydrogen (<b>1</b>, <b>3</b>–<b>14</b>), pyridine (<b>17</b>–<b>19</b>, <b>21</b>, <b>22</b>, <b>24</b>, <b>25</b>), para-methoxyphenyl (<b>27</b>, <b>28</b>, <b>30</b>, <b>32</b>–<b>34</b>), and thiophene (<b>35</b>–<b>38</b>). Variants of all <b>R2</b> subtypes with para-chloro at position <b>R1</b> are present in <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a>, allowing some measure of standardized comparison. Compound <b>28</b> (<b>R2</b>=para-methoxyphenyl) was only slightly more potent than <b>18</b> (<b>R2</b>=pyridine), indicating that there was not a significant difference between the two aromatic moieties (<b>R3</b>=cyclohexylamide for both). Compound <b>11</b> (<b>R1</b>=H) was also very similar in potency; however, the different <b>R3</b> group (ethyl trifluoroacetamide) can’t be discounted as having a tertiary effect on the overall potency. It is difficult to assess whether or not it is the thiophene or the phenylpropanamide of compound <b>36</b> that accounts for its somewhat tempered potency; however, overall, the <b>R2</b> position seems to give wide latitude to non-bulky aromatic structures (or absence thereof). Introduction of the different aromatic moieties to the structure of probe compound <b>1</b> will be addressed as part of ongoing SAR.</p><p><i><u>SAR of R3</u>:</i> This position has been the main focus of our SAR efforts. An amide moiety of some type seems to confer a measurable degree of potency, as aliphatic (<b>9</b>, <b>10</b>, <b>50</b>) or heterocyclic (<b>39</b>) analogs suffered from decreased potency. Regarding the probe compound <b>1</b>, there seemed to be some unique characteristics of the ethyl trifluoroacetamide that were lost upon replacement of the trifluoromethyl group by either an aromatic ring (<b>3</b>, <b>4</b>) methyl (<b>2</b>), or aliphatic alkyne (<b>5</b>). However, converting the acetamide nitrogen into a tertiary amine slightly enhanced potency (<b>6</b>). Optimal linker length between the alpha-chloroacetamide and the trifluoroacetamide moiety appears to be 4 carbons (<b>7</b>), with a slight decrease in potency observed with either 3 carbons (<b>1</b>) or 5 carbons (<b>8</b>). With regard to the other primary substituent present among library compounds, the cyclohexylamide, attempts to convert the cyclohexyl to alkyne derivatives met with poor success, as each proved to be somewhat less potent than its starting analog (<b>22</b> vs. <b>21</b>, <b>32</b> vs. <b>27</b>, <b>34</b> vs. <b>28</b>).</p><p>The hydrophobicity of the <b>R3</b> group seems to play a large role in compound selectivity as judged by the number of anti-target hits. Compound <b>10</b>, with a long aliphatic chain, has the most anti-targets (6 anti-targets at 10 μM test compound), followed by compound <b>35</b> (4 anti-targets at 10 μM test compound), which has a relatively long-chain phenylethylamide at <b>R3</b>. In general, the less hydrophobic trifluoroacetamides (<b>1</b>, <b>6</b>–<b>8</b>, <b>11</b>–<b>16</b>) are more selective (fewer anti-targets) than the cyclohexylamides (<b>17</b>–<b>21</b>, <b>23</b>–<b>31</b>). Hydrophobicity may also explain the relative selectivity between compounds <b>6</b>, <b>7</b> and <b>8</b>, where the compound with the longest methylene chain (<b>8</b>) is also the least selective (1 anti-target at 10 μM compared with none for <b>6</b> and <b>7</b>). Likewise, the hydrophobic hexynylamide of compound <b>22</b> may account for its comparative non-selectivity (2 anti-targets at 10 μM compared with none for compound <b>1</b>). Converting the cyclohexyl portion of the amide to more potent analogs, as well as varying the spacer length, will likely serve as future areas of SAR.</p><p><i><u>Summary</u>:</i> Following this SAR analysis, two synthetic analogs, <b>6</b> and <b>7,</b> emerged as more potent than the probe compound <b>1</b>. Additionally, neither <b>6</b> nor <b>7</b> show evidence of off-targets at 10 μM by competitive ABPP. Compound <b>6</b> was discounted as a possible probe due to the comparative intractability of its synthetic route. Compound <b>7</b> was a product of the latest round of SAR, and was not characterized until after compound <b>1</b> was designated as the probe compound; however, it could rightly have been deemed a probe compound as well.</p></div><div id="ml175.s24"><h3>3.5. Cellular Activity</h3><p>Probe compound <b>1</b> and numerous analogs (<b>5</b>, <b>6</b>, <b>17</b>, <b>21</b>, <b>22</b>, <b>25</b>, <b>27</b>, <b>32</b>, <b>35</b>; see <a class="figpopup" href="/books/NBK98917/table/ml175.t2/?report=objectonly" target="object" rid-figpopup="figml175t2" rid-ob="figobml175t2">Table 2</a> and <a class="figpopup" href="/books/NBK98917/figure/ml175.f11/?report=objectonly" target="object" rid-figpopup="figml175f11" rid-ob="figobml175f11">Supplemental Figure S4</a>) were highly active against GSTO1 <i>in situ</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463102</a>), indicating that the probe is free to cross cell membranes and inhibit its target in the cytoplasm of cells.</p><p>The probe compound <b>1</b> and analog <b>25</b> were also evaluated for cell toxicity (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449773" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449773</a>) using both serum-supplemented and serum-free media. As shown in <a class="figpopup" href="/books/NBK98917/figure/ml175.f4/?report=objectonly" target="object" rid-figpopup="figml175f4" rid-ob="figobml175f4">Figure 4</a> below, both compounds had CC<sub>50</sub>s >25 μM, which is well above the dose required to successfully inhibit GSTO1 (<100 nM <i>in vitro</i>, <1 μM <i>in situ</i>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f4" co-legend-rid="figlgndml175f4"><a href="/books/NBK98917/figure/ml175.f4/?report=objectonly" target="object" title="Figure 4" class="img_link icnblk_img figpopup" rid-figpopup="figml175f4" rid-ob="figobml175f4"><img class="small-thumb" src="/books/NBK98917/bin/ml175f4.gif" src-large="/books/NBK98917/bin/ml175f4.jpg" alt="Figure 4. Cytotoxicity of Probe and Probe Analog in Serum-supplemented (A) and Serum-free (B) media." /></a><div class="icnblk_cntnt" id="figlgndml175f4"><h4 id="ml175.f4"><a href="/books/NBK98917/figure/ml175.f4/?report=objectonly" target="object" rid-ob="figobml175f4">Figure 4</a></h4><p class="float-caption no_bottom_margin">Cytotoxicity of Probe and Probe Analog in Serum-supplemented (A) and Serum-free (B) media. </p></div></div></div><div id="ml175.s25"><h3>3.6. Profiling Assays</h3><p>To date, the probe compound <b>1</b> (CID 4257368) has been tested in 213 other bioassays deposited in PubChem, and has shown activity in only 4 of those assays, giving a hit rate of less than 2%, indicating that this compound is not generally active in a broad range of cell-based and non-cell based assays.</p></div><div id="ml175.s26"><h3>3.7. Click Chemistry (CC)-ABPP Characterization of Anti-targets</h3><p><b><i>In Vitro Analysis:</i></b> In addition to competitive ABPP assays for analysis of probe selectivity, we also directly assessed probe selectivity through CC-ABPP profiling of alkyne analogs both <i>in vitro</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463101" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463101</a>) and <i>in situ</i> (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463093" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">463093</a>). Both compound <b>6</b> and compound <b>5</b> have highly analogous structures to the probe compound <b>1</b>: in compound <b>6</b>, the <b>R3</b> group includes a tertiary propargyl amine, whereas in compound <b>5</b>, the trifluoroacetyl moiety has been replaced with an aliphatic alkyne. An alkyne is used rather than a fluorophore to minimize structural perturbation. As designed, after reaction with protein targets, these alkyne analogs can be labeled with a fluorophore-conjugated azide using the copper(I)-catalyzed azide-alkyne cycloaddition click reaction [<a class="bk_pop" href="#ml175.r14">14</a>]. Compound <b>6</b> has a similar potency to the probe compound (IC<sub>50</sub> of 23 nM vs 28 nM), and, as can be seen in <a class="figpopup" href="/books/NBK98917/figure/ml175.f5/?report=objectonly" target="object" rid-figpopup="figml175f5" rid-ob="figobml175f5">Figure 5</a>, has a similar dose response of GSTO1 inhibition as assessed by competitive ABPP with the SE-Rh probe (Panel B vs. A). (Note: the no-compound DMSO control is shown in lane 1, where the SE-Rh activity-based probe completely labels GSTO1, as indicated by the arrow). The potency of compound <b>5</b> is somewhat weaker than the probe compound <b>1</b> (Panel D vs. A). In panels C and E of <a class="figpopup" href="/books/NBK98917/figure/ml175.f5/?report=objectonly" target="object" rid-figpopup="figml175f5" rid-ob="figobml175f5">Figure 5</a> are shown the CC-ABPP reactivity profiles of compounds <b>6</b> and <b>5</b>, respectively. After protein labeling by the alkyne analog test compound, rhodamine-azide (Rh-N3) is appended to the alkyne moiety via CC. At higher (1 μM and 250 nM) concentrations, some non-specific labeling of abundant proteins is observed; however, at lower (63 nM and 16 nM) concentrations, the only target labeled by either alkyne analog is GSTO1. Due to the increased potency of compound <b>6</b> (vs. <b>5</b>), near-complete labeling of GSTO1 is sustained at the lower concentrations for the former. As such, there is an optimal range above the IC<sub>50</sub> of compound <b>6</b> were complete labeling of GSTO1 is achieved (panel B, 63 nM) without appreciably inhibiting any anti-targets (panel C, 63 nM). Given the structural similarity, profile, and potency of compound <b>6</b> and probe compound <b>1</b>, this result strongly suggests that the probe, likewise, can inhibit GSTO1 to near-completion without reacting with any anti-targets.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f5" co-legend-rid="figlgndml175f5"><a href="/books/NBK98917/figure/ml175.f5/?report=objectonly" target="object" title="Figure 5" class="img_link icnblk_img figpopup" rid-figpopup="figml175f5" rid-ob="figobml175f5"><img class="small-thumb" src="/books/NBK98917/bin/ml175f5.gif" src-large="/books/NBK98917/bin/ml175f5.jpg" alt="Figure 5. Competitive-ABPP vs. Click Chemistry (CC)-ABPP to assess probe and analog selectivity, MDA-MB-435 soluble proteome." /></a><div class="icnblk_cntnt" id="figlgndml175f5"><h4 id="ml175.f5"><a href="/books/NBK98917/figure/ml175.f5/?report=objectonly" target="object" rid-ob="figobml175f5">Figure 5</a></h4><p class="float-caption no_bottom_margin">Competitive-ABPP vs. Click Chemistry (CC)-ABPP to assess probe and analog selectivity, MDA-MB-435 soluble proteome. Fluorescent image shown in grey scale; band corresponding to GSTO1 is indicated by arrow; DMSO (no compound) control is shown in lane 1; <a href="/books/NBK98917/figure/ml175.f5/?report=objectonly" target="object" rid-ob="figobml175f5">(more...)</a></p></div></div><p><b><i>In Situ Analysis:</i></b> Comparison of the competitive-ABPP profile to the CC-ABPP profile of compound <b>6</b> in cultured MDA-MB-435 cells (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463093" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463093</a>) suggests that it is possible to achieve complete <i>in situ</i> inhibition of GSTO1 (<a class="figpopup" href="/books/NBK98917/figure/ml175.f6/?report=objectonly" target="object" rid-figpopup="figml175f6" rid-ob="figobml175f6">Figure 6</a><b>,</b> competitive-ABPP panel, 250 nM dose) with no anti-target effects (<a class="figpopup" href="/books/NBK98917/figure/ml175.f6/?report=objectonly" target="object" rid-figpopup="figml175f6" rid-ob="figobml175f6">Figure 6</a><b>,</b> CC-ABPP panel, 250 nM dose) with 250 nM compound treatment.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml175f6" co-legend-rid="figlgndml175f6"><a href="/books/NBK98917/figure/ml175.f6/?report=objectonly" target="object" title="Figure 6" class="img_link icnblk_img figpopup" rid-figpopup="figml175f6" rid-ob="figobml175f6"><img class="small-thumb" src="/books/NBK98917/bin/ml175f6.gif" src-large="/books/NBK98917/bin/ml175f6.jpg" alt="Figure 6. In Situ Inhibition Profile of Compound 6 (SID 96107583) by Competitive ABPP and Click Chemistry ABPP." /></a><div class="icnblk_cntnt" id="figlgndml175f6"><h4 id="ml175.f6"><a href="/books/NBK98917/figure/ml175.f6/?report=objectonly" target="object" rid-ob="figobml175f6">Figure 6</a></h4><p class="float-caption no_bottom_margin"><i>In Situ</i> Inhibition Profile of Compound <i>6</i> (SID 96107583) by Competitive ABPP and Click Chemistry ABPP. Fluorescent image shown in grey scale; band corresponding to GSTO1 indicated with arrow; DMSO (no compound) control is shown in lane 1; see AID 463093 <a href="/books/NBK98917/figure/ml175.f6/?report=objectonly" target="object" rid-ob="figobml175f6">(more...)</a></p></div></div></div></div><div id="ml175.s27"><h2 id="_ml175_s27_">4. Discussion</h2><p>Compound <b>1</b> (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>) was identified as a highly potent and selective covalent inhibitor of the target enzyme GSTO1. The probe has an IC<sub>50</sub> of 28 nM, and greater than 350-fold selectivity against potential anti-targets as assessed by competitive ABPP profiling. The probe has also been shown to be active <i>in situ</i>, completely inhibiting GSTO1 at 250 nM compound concentration. Additionally, we have synthesized several alkyne analogs of the probe compound. These analogs have been used to assess potential anti-targets not encompassed by competitive ABPP profiling by providing a direct readout of compound labeling. None of the probe analogs showed evidence of off-targets by CC-ABPP either <i>in vitro</i> or <i>in situ</i>, indicating that the alkyne analogs have no problematic anti-targets in the MDA-MB-435 human cancer cell line tested. This highly suggests that the probe compound itself, likewise, has no anti-target effects. Overall, this molecule has favorable stability (half-life of >48 hours in PBS), solubility (480 μM in PBS), and general reactivity [not reactive with glutathione, low (2%) activity in other PubChem bioassays) properties, and low cytotoxicity (CC<sub>50</sub> >25 μM). Taken together, these findings suggest that it is very possible to develop potent and selective probes based on tempered electrophilic scaffolds, and that compound <b>1</b> will be a highly successful probe for biochemical investigation of GSTO1.</p><div id="ml175.s28"><h3>4.1. Comparison to existing art and how the new probe is an improvement</h3><p>This probe compound <b>1</b> (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/99205797" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 99205797</a>) is 4 times more potent than the previously identified 120 nM lead alpha-chloroacetamide candidate [<a class="bk_pop" href="#ml175.r4">4</a>], and much more extensively characterized in terms of its toxicity, selectivity, <i>in situ</i> activity, stability, and solubility. It is worth noting that the 120 nM GSTO1 inhibitor was in the screening library and did score as a confirmed hit in the uHTS screen (compound <b>66</b>, <a class="figpopup" href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" rid-figpopup="figml175f7" rid-ob="figobml175f7">Figure 7</a>). However, not unexpectedly (given relatively moderate potency) it did not pass the secondary screening threshold set for 90% target inhibition at 1 μM in a complex proteome. The highly related structural analog <b>65</b> (bearing a para-methoxy instead of a para-isopropoxy on the <b>R2/R3</b> propyl dibenzene) was a more potent inhibitor, but suffered from a high anti-target hit rate at 10 μM.</p><p>Compound <b>1</b> is also ~2-fold more potent than a recently reported GSTO1 inhibitor, the cell labeling reagent CellTracker Green (<a class="figpopup" href="/books/NBK98917/figure/ml175.f7/?report=objectonly" target="object" rid-figpopup="figml175f7" rid-ob="figobml175f7">Figure 7</a>); additionally, the probe does not undergo esterase metabolism as does CellTracker Green, which renders the dye cell-impermeable [<a class="bk_pop" href="#ml175.r5">5</a>].</p></div><div id="ml175.s29"><h3>4.2. Mechanism of Action Studies</h3><p>As determined from LC-MS/MS analysis (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/449772" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 449772</a>), the probe is an activity-based inhibitor; it covalently labels the active site cysteine nucleophile, Cys32 [<a class="bk_pop" href="#ml175.r1">1</a>], of GSTO1. The observed mass shift of the active site peptide suggests that reaction occurs via cysteine nucleophilic attack to displace the chloride, as expected of this chemotype. Because of the secondary screening methodology employed – competitive ABPP profiling with active-site directed activity-based probes – we can directly link inhibition of GSTO1 by the probe compound <b>1</b> to a corresponding loss of enzymatic activity.</p></div><div id="ml175.s30"><h3>4.3. Planned Future Studies</h3><p>Currently, we are further investigating the SAR of the probe through synthesis of additional analogs. This probe and its analogs are being evaluated in cell-based assays, including assessing whether or not inhibition of GSTO1 enhances the sensitivity of cancer cells to chemotherapeutic reagents [<a class="bk_pop" href="#ml175.r2">2</a>]. The effects of probe treatment on cancer cell proliferation, migration, and invasion will also be evaluated. If these experiments suggest that inhibiting GSTO1 with the probe compound is positively correlated with enhanced efficacy of chemotherapeutic reagents and/or reduced cancer cell aggressiveness, future studies will assess <i>in vivo</i> inhibition of GSTO1 in mouse xenograft tumor models [<a class="bk_pop" href="#ml175.r15">15</a>]. If the probe proves unsuitable for <i>in vivo</i> studies, additional rounds of SAR will be aimed at improving probe bioavailability.</p></div></div><div id="ml175.s31"><h2 id="_ml175_s31_">5. References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="ml175.r1">Adam GC, et al. Mapping enzyme active sites in complex proteomes. <span><span class="ref-journal">J. Am. Chem. Soc. </span>2004;<span class="ref-vol">126</span>(5):1363–1368.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14759193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14759193</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="ml175.r2">Yan XD, et al. Identification of platinum-resistance associated proteins through proteomic analysis of human ovarian cancer cells and their platinum-resistant sublines. <span><span class="ref-journal">J. Proteome Res. </span>2007;<span class="ref-vol">6</span>(2):772–780.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17269733" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17269733</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="ml175.r3">Adam GC, Sorensen EJ, Cravatt BF. Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype. <span><span class="ref-journal">Nat. Biotechnol. </span>2002;<span class="ref-vol">20</span>(8):805–809.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12091914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12091914</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="ml175.r4">Bachovchin DA, et al. Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes. <span><span class="ref-journal">Nat. Biotechnol. </span>2009;<span class="ref-vol">27</span>(4):387–394.</span> [<a href="/pmc/articles/PMC2709489/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2709489</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19329999" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19329999</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="ml175.r5">Son J, et al. Isozyme-specific fluorescent inhibitor of glutathione s-transferase omega 1. <span><span class="ref-journal">ACS Chem. Biol. </span>2010;<span class="ref-vol">5</span>(5):449–453.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20205472" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20205472</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="ml175.r6">Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. <span><span class="ref-journal">Annu. Rev. Pharmacol. Toxicol. </span>2005;<span class="ref-vol">45</span>:51–88.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15822171" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15822171</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="ml175.r7">Whitbread AK, et al. Characterization of the omega class of glutathione transferases. <span><span class="ref-journal">Methods Enzymol. </span>2005;<span class="ref-vol">401</span>:78–99.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16399380" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16399380</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="ml175.r8">Board PG, et al. S-(4-Nitrophenacyl)glutathione is a specific substrate for glutathione transferase omega 1-1. <span><span class="ref-journal">Anal. Biochem. </span>2008;<span class="ref-vol">374</span>(1):25–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18028863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18028863</span></a>]</div></dd><dt>9.</dt><dd><div class="bk_ref" id="ml175.r9">Weerapana E, Simon GM, Cravatt BF. Disparate proteome reactivity profiles of carbon electrophiles. <span><span class="ref-journal">Nat Chem Biol. </span>2008;<span class="ref-vol">4</span>(7):405–407.</span> [<a href="/pmc/articles/PMC2440582/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2440582</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18488014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18488014</span></a>]</div></dd><dt>10.</dt><dd><div class="bk_ref" id="ml175.r10">Leung D, et al. Discovering potent and selective reversible inhibitors of enzymes in complex proteomes. <span><span class="ref-journal">Nat Biotechnol. </span>2003;<span class="ref-vol">21</span>(6):687–691.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12740587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12740587</span></a>]</div></dd><dt>11.</dt><dd><div class="bk_ref" id="ml175.r11">Johnson DS, Weerapana E, Cravatt BF. Strategies for discovering and derisking covalent, irreversible enzyme inhibitors. <span><span class="ref-journal">Future Med. Chem. </span>2010;<span class="ref-vol">2</span>(6):949–964.</span> [<a href="/pmc/articles/PMC2904065/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2904065</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20640225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20640225</span></a>]</div></dd><dt>12.</dt><dd><div class="bk_ref" id="ml175.r12">Vincent PW, et al. Anticancer efficacy of the irreversible EGFr tyrosine kinase inhibitor PD 0169414 against human tumor xenografts. <span><span class="ref-journal">Cancer Chemother. Pharmacol. </span>2000;<span class="ref-vol">45</span>(3):231–238.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10663641" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10663641</span></a>]</div></dd><dt>13.</dt><dd><div class="bk_ref" id="ml175.r13">Robertson JG. Mechanistic basis of enzyme-targeted drugs. <span><span class="ref-journal">Biochemistry. </span>2005;<span class="ref-vol">44</span>(15):5561–5571.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15823014" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15823014</span></a>]</div></dd><dt>14.</dt><dd><div class="bk_ref" id="ml175.r14">Speers AE, Cravatt BF. Profiling enzyme activities in vivo using click chemistry methods. <span><span class="ref-journal">Chem. Biol. </span>2004;<span class="ref-vol">11</span>(4):535–546.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15123248" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15123248</span></a>]</div></dd><dt>15.</dt><dd><div class="bk_ref" id="ml175.r15">Jessani N, et al. Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo. <span><span class="ref-journal">Proc. Natl. Acad. Sci. U.S.A. </span>2004;<span class="ref-vol">101</span>(38):13756–13761.</span> [<a href="/pmc/articles/PMC518829/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC518829</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15356343" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15356343</span></a>]</div></dd></dl></div><div id="ml175.s32"><h2 id="_ml175_s32_">Supplemental SAR Tables</h2><p id="ml175.t4"><a href="/books/NBK98917/table/ml175.t4/?report=objectonly" target="object">Table S1. SAR Analysis for Target: Other R2=H</a></p><p id="ml175.t5"><a href="/books/NBK98917/table/ml175.t5/?report=objectonly" target="object">Table S2. SAR Analysis for Target: R2/R3 = cyclo</a></p><p id="ml175.t6"><a href="/books/NBK98917/table/ml175.t6/?report=objectonly" target="object">Table S3. SAR Analysis for Target: Benzyl sub for Phenyl</a></p><p id="ml175.t7"><a href="/books/NBK98917/table/ml175.t7/?report=objectonly" target="object">Table S4. SAR Analysis for Target: Non Aromatic sub for Phenyl</a></p><p id="ml175.t8"><a href="/books/NBK98917/table/ml175.t8/?report=objectonly" target="object">Table S5. SAR Analysis for Target: Ring-Constrained acetamides</a></p><p id="ml175.ts6"><a href="/books/NBK98917/table/ml175.ts6/?report=objectonly" target="object">Table S6. SAR Analysis for Target: Aryl-Chlorides</a></p><p id="ml175.t9"><a href="/books/NBK98917/table/ml175.t9/?report=objectonly" target="object">Table S7. SAR Analysis for Target: Epoxides</a></p></div><div id="ml175.s32b"><h2 id="_ml175_s32b_">Supplemental Figures</h2><p id="ml175.f8"><a href="/books/NBK98917/figure/ml175.f8/?report=objectonly" target="object">Figure S1. 1<sup>st</sup> Round Secondary Screening: Competitive-ABPP profiling with recombinant GSTO1: 1 μM test compound, SE-Rh probe</a></p><p id="ml175.f9"><a href="/books/NBK98917/figure/ml175.f9/?report=objectonly" target="object">Figure S2. 2<sup>nd</sup> Round Secondary Screening: Competitive-ABPP profiling with endogenous GSTO1: uHTS Hits, 1 μM test compound, SE-Rh probe, MDA-MB-435 soluble proteome</a></p><p id="ml175.f10"><a href="/books/NBK98917/figure/ml175.f10/?report=objectonly" target="object">Figure S3. 3<sup>rd</sup> Round Secondary Screening: Competitive-ABPP profiling with endogenous GSTO1 in MDA-MB-435 soluble proteome</a></p><p id="ml175.f11"><a href="/books/NBK98917/figure/ml175.f11/?report=objectonly" target="object">Figure S4. 4<sup>th</sup> Round of Secondary Screening: Inhibition of GSTO1 in situ, 1 μM compound, MDA-MB-435 Cells in Culture</a></p><p id="ml175.f12"><a href="/books/NBK98917/figure/ml175.f12/?report=objectonly" target="object">Figure S5. Competitive-ABPP profiling with endogenous GSTO1 in MDA-MB-435 soluble proteome: Synthetic Analogs</a></p></div><div style="display:none"><div style="display:none" id="figml175f8"><img alt="Image ml175f8" src-large="/books/NBK98917/bin/ml175f8.jpg" /></div><div style="display:none" id="figml175f9"><img alt="Image ml175f9a" src-large="/books/NBK98917/bin/ml175f9a.jpg" /></div><div style="display:none" id="figml175f10"><img alt="Image ml175f10a" src-large="/books/NBK98917/bin/ml175f10a.jpg" /></div><div style="display:none" id="figml175f11"><img alt="Image ml175f11" src-large="/books/NBK98917/bin/ml175f11.jpg" /></div><div style="display:none" id="figml175f12"><img alt="Image ml175f12a" src-large="/books/NBK98917/bin/ml175f12a.jpg" /></div></div><div id="bk_toc_contnr"></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK98917/?report=reader">PubReader</a></li><li><a href="/books/NBK98917/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK98917" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK98917" style="display:none" title="Cite this Page"><div class="bk_tt">Tsuboi K, Bachovchin DA, Speers AE, et al. Optimization and Characterization of an Inhibitor for Glutathione S-Tranferase Omega 1 (GSTO1) 2010 Aug 31 [Updated 2011 Dec 12]. 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></div></div></li><li><a href="/books/NBK98917/pdf/Bookshelf_NBK98917.pdf">PDF version of this page</a> (4.4M)</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#ml175.s1" ref="log$=inpage&link_id=inpage">Probe Structure & Characteristics</a></li><li><a href="#ml175.s2" ref="log$=inpage&link_id=inpage">Recommendations for scientific use of the probe</a></li><li><a href="#ml175.s3" ref="log$=inpage&link_id=inpage">Introduction</a></li><li><a href="#ml175.s4" ref="log$=inpage&link_id=inpage">Materials and Methods</a></li><li><a href="#ml175.s19" ref="log$=inpage&link_id=inpage">Results</a></li><li><a href="#ml175.s27" ref="log$=inpage&link_id=inpage">Discussion</a></li><li><a href="#ml175.s31" ref="log$=inpage&link_id=inpage">References</a></li><li><a href="#ml175.s32" ref="log$=inpage&link_id=inpage">Supplemental SAR Tables</a></li><li><a href="#ml175.s32b" ref="log$=inpage&link_id=inpage">Supplemental Figures</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=2961606" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcassay&DbFrom=books&Cmd=Link&LinkName=books_pcassay_probe&IdsFromResult=2961606" ref="log$=recordlinks">PubChem BioAssay for Chemical Probe</a><div class="brieflinkpop offscreen_noflow">PubChem BioAssay records reporting screening data for the development of the chemical probe(s) described in this book chapter</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcsubstance&DbFrom=books&Cmd=Link&LinkName=books_pcsubstance&IdsFromResult=2961606" ref="log$=recordlinks">PubChem Substance</a><div class="brieflinkpop offscreen_noflow">Related PubChem Substances</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=2961606" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21899313" ref="ordinalpos=1&linkpos=1&log$=relatedarticles&logdbfrom=pubmed">Potent and selective inhibitors of glutathione S-transferase omega 1 that impair cancer drug resistance.</a><span class="source">[J Am Chem Soc. 2011]</span><div class="brieflinkpop offscreen_noflow">Potent and selective inhibitors of glutathione S-transferase omega 1 that impair cancer drug resistance.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Tsuboi K, Bachovchin DA, Speers AE, Spicer TP, Fernandez-Vega V, Hodder P, Rosen H, Cravatt BF. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Am Chem Soc. 2011 Oct 19; 133(41):16605-16. 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Epub 2016 Oct 5.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/23658953" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimization and characterization of a triazole urea inhibitor for alpha/beta hydrolase domain-containing protein 11 (ABHD11): anti-probe for LYPLA1/LYPLA2 dual inhibitor ML211.</a><span class="source">[Probe Reports from the NIH Mol...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Optimization and characterization of a triazole urea inhibitor for alpha/beta hydrolase domain-containing protein 11 (ABHD11): anti-probe for LYPLA1/LYPLA2 dual inhibitor ML211.<div class="brieflinkpopdesc"><em 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