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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="Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2010/09/02" /><meta name="citation_author" content="Eduard Sergienko" /><meta name="citation_author" content="Xochella Garcia" /><meta name="citation_author" content="Brock Brown" /><meta name="citation_author" content="Justin Rascon" /><meta name="citation_author" content="Sonoko Narisawa" /><meta name="citation_author" content="Ana Maria Simao" /><meta name="citation_author" content="José Luis Millán" /><meta name="citation_author" content="Derek Stonich" /><meta name="citation_author" content="Ying Su" /><meta name="citation_author" content="Pasha Khan" /><meta name="citation_author" content="Greg Roth" /><meta name="citation_author" content="Layton Smith" /><meta name="citation_author" content="Shakeela Dad" /><meta name="citation_author" content="Thomas DY Chung" /><meta name="citation_author" content="Nicholas DP Cosford" /><meta name="citation_pmid" content="21433359" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK47343/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Eduard Sergienko" /><meta name="DC.Contributor" content="Xochella Garcia" /><meta name="DC.Contributor" content="Brock Brown" /><meta name="DC.Contributor" content="Justin Rascon" /><meta name="DC.Contributor" content="Sonoko Narisawa" /><meta name="DC.Contributor" content="Ana Maria Simao" /><meta name="DC.Contributor" content="José Luis Millán" /><meta name="DC.Contributor" content="Derek Stonich" /><meta name="DC.Contributor" content="Ying Su" /><meta name="DC.Contributor" content="Pasha Khan" /><meta name="DC.Contributor" content="Greg Roth" /><meta name="DC.Contributor" content="Layton Smith" /><meta name="DC.Contributor" content="Shakeela Dad" /><meta name="DC.Contributor" content="Thomas DY Chung" /><meta name="DC.Contributor" content="Nicholas DP Cosford" /><meta name="DC.Date" content="2010/09/02" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK47343/" /><meta name="description" content="Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML085 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP." /><meta name="og:title" content="Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1" /><meta name="og:type" content="book" /><meta name="og:description" content="Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML085 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK47343/" /><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/ml085/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK47343/" /><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="/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="#__NBK47343_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK47343_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/ml086/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml084/" 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="_NBK47343_"><span class="title" itemprop="name">Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1</span></h1><p class="contrib-group"><span itemprop="author">Eduard Sergienko</span>, <span itemprop="author">Xochella Garcia</span>, <span itemprop="author">Brock Brown</span>, <span itemprop="author">Justin Rascon</span>, <span itemprop="author">Sonoko Narisawa</span>, <span itemprop="author">Ana Maria Simao</span>, <span itemprop="author">José Luis Millán</span>, <span itemprop="author">Derek Stonich</span>, <span itemprop="author">Ying Su</span>, <span itemprop="author">Pasha Khan</span>, <span itemprop="author">Greg Roth</span>, <span itemprop="author">Layton Smith</span>, <span itemprop="author">Shakeela Dad</span>, <span itemprop="author">Thomas DY Chung</span>, and <span itemprop="author">Nicholas DP Cosford</span>.</p><p class="small">Received: <span itemprop="datePublished">April 18, 2009</span>; Last Update: <span itemprop="dateModified">September 2, 2010</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>Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function and relevance are still unknown, but PLAP-like enzymes are detected in serum of patients with primary testicular tumors, in particular seminoma and other cancers. Consequently, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) may provide the necessary tools to characterize its biological role. Currently, inhibitors of PLAP lack either potency or selectivity. The small molecule probe ML085 (CID-25067483) is a biochemical inhibitor of PLAP, and will be useful to elucidate the key biological functions and natural substrates of human PLAP.</p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> 1 R03 MH077602-01</p><p><b>Screening Center Name & PI:</b>
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<i>Conrad Prebys</i> Center for Chemical Genomics (<i>formerly Burnham Center for Chemical Genomics</i>) & Dr. John C. Reed</p><p><b>Chemistry Center Name & PI:</b>
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<i>Conrad Prebys</i> Center for Chemical Genomics (<i>formerly Burnham Center for Chemical Genomics)</i> & Dr. John C. Reed</p><p><b>Assay Submitter & Institution:</b> Dr José Luis Millán & Sanford-Burnham Medical Research Institute (<i>formerly Burnham Institute for Medical Research</i>)</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1577</a></p><div id="ml085.s2"><h2 id="_ml085_s2_">Probe Structure & Characteristics</h2><div id="ml085.fu1" class="figure"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu1.jpg" alt="Image ml085fu1" /></div></div><div id="ml085.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml085.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID/ML</th><th id="hd_h_ml085.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Target Name</th><th id="hd_h_ml085.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC50/EC50 (nM) [SID, AID]</th><th id="hd_h_ml085.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Anti-target Name(s)</th><th id="hd_h_ml085.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IC50/EC50 (μM) [SID, AID]</th><th id="hd_h_ml085.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Selectivity</th><th id="hd_h_ml085.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Secondary Assay(s) Name: IC50/EC50 (nM) [SID, AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml085.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-665093<br /><br />
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<a href="/pcsubstance/?term=ML085[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML085</a></td><td headers="hd_h_ml085.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PLAP</td><td headers="hd_h_ml085.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2,600 nM IC<sub>50</sub>
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373725" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373725</a>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1512" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1512</a></td><td headers="hd_h_ml085.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TNAP</td><td headers="hd_h_ml085.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100 µM IC<sub>50</sub>
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373725" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373725</a>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/518" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-518</a></td><td headers="hd_h_ml085.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">> 42</td><td headers="hd_h_ml085.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td headers="hd_h_ml085.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml085.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml085.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td><td headers="hd_h_ml085.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IAP</td><td headers="hd_h_ml085.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>6.25 µM IC<sub>50</sub>
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373725" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373725</a>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1017" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1017</a></td><td headers="hd_h_ml085.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>2.4</td><td headers="hd_h_ml085.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"></td></tr></tbody></table></div></div></div><div id="ml085.s3"><h2 id="_ml085_s3_">Recommendations for the scientific use of this probe</h2><p>Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function is still unknown (<a class="bk_pop" href="#ml085.r1">1</a>,<a class="bk_pop" href="#ml085.r2">2</a>). PLAP-like enzymes could be detected in serum of patients with primary testicular tumors, in particular seminoma (<a class="bk_pop" href="#ml085.r3">3</a>) and other cancers (<a class="bk_pop" href="#ml085.r4">4</a>). This PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) can be used as a tools to characterize the biological role of PLAP. The small molecule probe CID-665093 will be useful to elucidate the key biological functions and natural substrates of human placental alkaline phosphatase (PLAP)</p></div><div id="ml085.s4"><h2 id="_ml085_s4_">1. Scientific Rationale for Project</h2><p>Alkaline phosphatases (EC 3.1.3.1) (APs) catalyze the hydrolysis of phosphomonoesters, releasing phosphate and alcohol. APs are dimeric enzymes found in most organisms. In human, four isozymes of APs have been identified: three isozymes are tissue-specific and the fourth one is tissue-nonspecific. Placental alkaline phosphatase (PLAP) is highly expressed in primate placental tissue. Its biological function is still unknown. However, the identification of PLAP-specific inhibitors with selectivity over tissue non-specific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP) will provide the necessary tools to characterize its biological role</p></div><div id="ml085.s5"><h2 id="_ml085_s5_">2. Project Description</h2><div id="ml085.s6"><h3>a. The original goal for probe characteristics</h3><p>This MLSCN carry-forward project was an early Cycle 2 assay proposal and a formal CPDP was not filed. It was derived on work with tissue non-specific alkaline phoshatase inhibitor and later activator work, that suggested that PLAP specific inhibitors would also useful tools for this class of isozyme with yet to be elucidated biological function.</p></div><div id="ml085.s7"><h3>b. Assay implementation and screening</h3><div id="ml085.s8"><h4>i. PubChem Bioassay Name(s), AID(s), Assay-Type (Primary, DR, Counterscreen, Secondary)</h4><div id="ml085.tu2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.tu2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.tu2_lrgtbl__"><table><thead><tr><th id="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PubChem BioAssay Name</th><th id="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AIDs</th><th id="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe Type</th><th id="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Type</th><th id="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Format</th><th id="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Assay Detection & well format</th></tr></thead><tbody><tr><td headers="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Luminescent assay for HTS discovery of chemical inhibitors of placental alkaline phosphatase</td><td headers="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/690" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">690</a></td><td headers="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary</td><td headers="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (1536)</td></tr><tr><td headers="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Luminescent assay for HTS discovery of chemical inhibitors of placental alkaline phosphatase confirmation</td><td headers="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1512" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1512</a></td><td headers="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmatory</td><td headers="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Biochemical</td><td headers="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (384)</td></tr><tr><td headers="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TNAP luminescent HTS assay [Confirmatory]</td><td headers="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/518" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">518</a></td><td headers="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary Assay for specificity</td><td headers="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">biochemical</td><td headers="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (384)</td></tr><tr><td headers="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Luminescent assay for identification of inhibitors of human intestinal alkaline phosphatase [Confirmatory]</td><td headers="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1017" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1017</a></td><td headers="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreen Assay for specificity</td><td headers="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">biochemical</td><td headers="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (1536)</td></tr><tr><td headers="hd_h_ml085.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Luminescent assay for identification of inhibitors of bovine intestinal alkaline phosphatase [Primary Screening]</td><td headers="hd_h_ml085.tu2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1019" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1019</a></td><td headers="hd_h_ml085.tu2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inhibitor</td><td headers="hd_h_ml085.tu2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreen Assay for specificity</td><td headers="hd_h_ml085.tu2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">biochemical</td><td headers="hd_h_ml085.tu2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Luminescence (1536)</td></tr></tbody></table></div></div><p>Primary assay details are described below.</p><p>PLAP screening was developed and performed at the Burnham Center for Chemical Genomics (BCCG) within the Molecular Library Screening Center Network (MLSCN) as a selectivity screen for tissue nonspecific alkaline phosphatase (TNAP, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/518" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-518</a>). XO1 MH077602-01, Pharmacological inhibitors of tissue-nonspecific alkaline phosphatase (TNAP), Assay Provider Dr. José Luis Millán, Burnham Institute for Medical Research, La Jolla, CA.</p><div id="ml085.s9"><h5>Protocol</h5><div id="ml085.s10"><h5>PLAP assay materials</h5><ol><li class="half_rhythm"><div>PLAP protein was provided by Dr. José Luis Millán (Burnham Institute for Medical Research, San Diego, CA). The CDP-star was obtained from New England Biolabs.</div></li><li class="half_rhythm"><div>Assay Buffer: 250 mM DEA, pH 9.8, 2.5 mM MgCl<sub>2</sub>, and 0.05 mM ZnCl<sub>2</sub>.</div></li><li class="half_rhythm"><div>PLAP working solution contained a 1/6400 dilution in assay buffer. The solution was prepared fresh prior to use.</div></li><li class="half_rhythm"><div>CDP-star working solution contained 212.5 µM CDP-star in MQ water.</div></li><li class="half_rhythm"><div>TCEP working solution −5 mM in 10% DMSO.</div></li></ol></div><div id="ml085.s11"><h5>PLAP HTS protocol</h5><ol><li class="half_rhythm"><div>4 uL of 100 µM compounds in 10% DMSO were dispensed in columns 3–24 of Greiner 384-well white small volume plates (784075).</div></li><li class="half_rhythm"><div>Using a Thermo wellmate dispenser 4 uL of the following solutions were added:</div><ol class="lower-alpha"><li class="half_rhythm"><div>TCEP working solution - column 1 (positive control).</div></li><li class="half_rhythm"><div>10% DMSO - column 2 (negative control).</div></li></ol></li><li class="half_rhythm"><div>8 uL of PLAP working solution was added to the whole plate using a WellMate bulk dispenser (Matrix).</div></li><li class="half_rhythm"><div>8 uL of CDP-star working solution was added to the whole plate using WellMate bulk reagent dispenser (Matrix).</div></li><li class="half_rhythm"><div>Final concentrations of the components in the assay were as follows:</div><ol class="lower-alpha"><li class="half_rhythm"><div>100 mM DEA, pH 9.8, 1.0 mM MgCl<sub>2</sub>, 0.02 mM ZnCl<sub>2</sub> (columns 1–24)</div></li><li class="half_rhythm"><div>1/16000 dilution PLAP (columns 1–24)</div></li><li class="half_rhythm"><div>85 µM CDP-star (columns 1–24)</div></li><li class="half_rhythm"><div>1 mM TCEP (columns 1)</div></li><li class="half_rhythm"><div>2 % DMSO (columns 1–24)</div></li><li class="half_rhythm"><div>20 µM compounds (columns 3–24)</div></li></ol></li><li class="half_rhythm"><div>Plates were incubated for 30 minutes at room temperature.</div></li><li class="half_rhythm"><div>Luminescence was measured on an Envision plate reader (Perkin Elmer).</div></li><li class="half_rhythm"><div>Data analysis was performed using CBIS software (ChemInnovations, Inc).</div></li></ol></div></div><div id="ml085.s12"><h5>PLAP dose-response confirmation screening protocol</h5><ol><li class="half_rhythm"><div>Dose-response curves contained 10 concentrations of compounds obtained using 2-fold serial dilution. Compounds were serially diluted in 100% DMSO, and then diluted with water to 10% final DMSO concentration. 4 uL compounds in 10% DMSO were transferred into columns 3–22 of Greiner 384-well white small-volume plates (784075). Columns 1–2 and 23–24 contained 4 uL of TCEP working solution and 10% DMSO, respectively.</div></li><li class="half_rhythm"><div>8 uL of PLAP working solution was added to the whole plate using a WellMate bulk reagent dispenser (Matrix).</div></li><li class="half_rhythm"><div>8 uL of CDP-star working solution was added to the whole plate using a WellMate reagent bulk dispenser (Matrix).</div></li><li class="half_rhythm"><div>Plates were incubated for 30 mins at room temperature.</div></li><li class="half_rhythm"><div>Luminescence was measured on an Envision plate reader (Perkin Elmer).</div></li><li class="half_rhythm"><div>Data analysis was performed using CBIS software (ChemInnovations, Inc) using a sigmoidal dose-response equation through non-linear regression</div></li></ol></div></div><div id="ml085.s13"><h4>ii. Assay Rationale & Description</h4><p>For the assay rationale, description and reagents protocols see section 2a above.</p><p>For this screen 95857 compounds were tested. The average Z′ for the assay was 0.69, the average signal to background was 38.6, the average signal to noise was 122.7 and the average signal window was 7.8. Initially 192 compounds were identified as primary positives with >= 50% inhibition of activity in the assay. After performing dose-response experiments with liquid DMSO stocks of these compounds, 82 of the hits generated a dose-response curve.</p></div><div id="ml085.s14"><h4>iii. Summary of Results</h4><p>Primary hits from the PLAP HTS assay were confirmed and tested in parallel against TNAP for selectivity. A few selective hits were identified. Those hits were purchased along with 56 analogues (<a class="figpopup" href="/books/NBK47343/table/ml085.t1/?report=objectonly" target="object" rid-figpopup="figml085t1" rid-ob="figobml085t1">Table 1</a>). There are many commercial analogues available and so Analogue-By-Catalogue (ABC) was performed in an iterative fashion. From the purchased compounds we were able to conclude that the dihydroxyl groups of the catechol are essential for PLAP activity. The SAR was completed and a probe molecule CID-665093 (MLS-0014097) was identified (see <a class="figpopup" href="/books/NBK47343/table/ml085.t1/?report=objectonly" target="object" rid-figpopup="figml085t1" rid-ob="figobml085t1">Table 1</a> below).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml085t1"><a href="/books/NBK47343/table/ml085.t1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figml085t1" rid-ob="figobml085t1"><img class="small-thumb" src="/books/NBK47343/table/ml085.t1/?report=thumb" src-large="/books/NBK47343/table/ml085.t1/?report=previmg" alt="Table 1. SAR results generated using analogue-by-catalogue (ABC)." /></a><div class="icnblk_cntnt"><h4 id="ml085.t1"><a href="/books/NBK47343/table/ml085.t1/?report=objectonly" target="object" rid-ob="figobml085t1">Table 1</a></h4><p class="float-caption no_bottom_margin">SAR results generated using analogue-by-catalogue (ABC). </p></div></div><p>Medicinal chemistry focused on the two final probe candidates, CID-2102207 (MLS-0107074) and CID-665093 (MLS-0014097) (<a class="figpopup" href="/books/NBK47343/figure/ml085.f1/?report=objectonly" target="object" rid-figpopup="figml085f1" rid-ob="figobml085f1">Figure 1</a>) that were identified as low-micromolar inhibitors of PLAP through primary screening.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml085f1" co-legend-rid="figlgndml085f1"><a href="/books/NBK47343/figure/ml085.f1/?report=objectonly" target="object" title="Figure 1" class="img_link icnblk_img figpopup" rid-figpopup="figml085f1" rid-ob="figobml085f1"><img class="small-thumb" src="/books/NBK47343/bin/ml085f1.gif" src-large="/books/NBK47343/bin/ml085f1.jpg" alt="Figure 1" /></a><div class="icnblk_cntnt" id="figlgndml085f1"><h4 id="ml085.f1"><a href="/books/NBK47343/figure/ml085.f1/?report=objectonly" target="object" rid-ob="figobml085f1">Figure 1</a></h4></div></div><p>Re-synthesis of these targets was undertaken and these compounds were subjected to the BCCG target independent ADME assay panel (see also <a class="figpopup" href="/books/NBK47343/table/ml085.t1/?report=objectonly" target="object" rid-figpopup="figml085t1" rid-ob="figobml085t1">Table 1</a> below)</p></div></div><div id="ml085.s15"><h3>c. Probe Optimization</h3><div id="ml085.s16"><h4>Description of SAR & chemistry strategy (including structure and data) that led to the probe</h4><p>SAR was developed primarily by the ABC approach for this MLSCN project due to the availability of numerous commercial analogues. Analysis of the SAR identified some key structural features, including: (1) Reposition or derivatization of the hydroxyl groups leads to inactive compounds (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373705" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373705</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373700" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373700</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373696" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373696</a>). (2) Selectivity for PLAP apparently resides in the N-substituted triazole group (<a class="figpopup" href="/books/NBK47343/figure/ml085.f1/?report=objectonly" target="object" rid-figpopup="figml085f1" rid-ob="figobml085f1">Figure 1</a>). Unsubstituted triazoles also potently inhibit PLAP but do not display selectivity vs. TNAP and IAP. Though 58 analogues were purchased to explore R1 and R2 (see <a class="figpopup" href="/books/NBK47343/figure/ml085.f2/?report=objectonly" target="object" rid-figpopup="figml085f2" rid-ob="figobml085f2">Figure 2</a>, and attached triazole list at end), no significant improvement in either selectivity or potency was achieved. For example, analogue <a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287606" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-57287606</a> is in the submicromolar range for PLAP, but it is not as selective as the proposed probe molecule. The objective of chemistry was to develop a tractable route for the synthesis of the probe candidates, prepare authentic samples, confirm structure and purity, and provide enough material for submission to MLSMR.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml085f2" co-legend-rid="figlgndml085f2"><a href="/books/NBK47343/figure/ml085.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml085f2" rid-ob="figobml085f2"><img class="small-thumb" src="/books/NBK47343/bin/ml085f2.gif" src-large="/books/NBK47343/bin/ml085f2.jpg" alt="Figure 2. Probe analogs R1 & R2 variations." /></a><div class="icnblk_cntnt" id="figlgndml085f2"><h4 id="ml085.f2"><a href="/books/NBK47343/figure/ml085.f2/?report=objectonly" target="object" rid-ob="figobml085f2">Figure 2</a></h4><p class="float-caption no_bottom_margin">Probe analogs R1 & R2 variations. </p></div></div></div></div></div><div id="ml085.s17"><h2 id="_ml085_s17_">3. Probe</h2><div id="ml085.s18"><h3>a. Chemical name</h3><p>1-(3,4-dihydroxyphenyl)-2-[[5-(2-methoxyphenyl)-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]ethanone <b>[<a href="/pcsubstance/?term=ML085[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML085</a>]</b></p></div><div id="ml085.s19"><h3>b. Probe chemical structure</h3><div id="ml085.f3" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47343/bin/ml085f3.jpg" alt="Figure 3. Probe compound structure." /></div><h3><span class="label">Figure 3</span><span class="title">Probe compound structure</span></h3></div></div><div id="ml085.s20"><h3>c. Structural Verification Information of probe SID</h3><p><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373725" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-56373725</a></p><p>Spectral data supporting proposed structure: <sup>1</sup>H NMR (400 MHz, Acetone-D6) δ 7.54 (ddd, <i>J</i> = 8.4, 7.5, 1.8, 1H), 7.46 – 7.33 (m, 3H), 7.17 (d, <i>J</i> = 8.1, 1H), 7.07 (dt, <i>J</i> = 7.5, 0.9, 1H), 6.72 (d, <i>J</i> = 8.2, 1H), 5.89 – 5.60 (m, 1H), 5.10 (dd, <i>J</i> = 10.4, 1.1, 1H), 4.91 (dd, <i>J</i> = 17.2, 1.1, 1H), 4.78 (s, 2H), 4.49 (dd, <i>J</i> = 3.7, 1.6, 2H), 3.83 (s, 3H). <sup>13</sup>C NMR (101 MHz, Acetone-D6) δ 191.32, 159.49, 158.26, 154.41, 151.21, 148.89, 133.16, 132.97, 132.87, 124.45, 123.57, 121.53, 117.97, 117.73, 115.86, 113.80, 112.18, 55.92, 47.44, 42.01. MS (ESI) calculated C<sub>20</sub>H<sub>19</sub>N<sub>3</sub>O<sub>4</sub>S <i>m/z</i> = 397.11, found <i>m/z</i> = 398.01 [M+H].</p><div id="ml085.f4" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47343/bin/ml085f4.jpg" alt="Figure 4. NMR or Probe compound." /></div><h3><span class="label">Figure 4</span><span class="title">NMR or Probe compound</span></h3></div><div id="ml085.f5" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47343/bin/ml085f5.jpg" alt="Figure 5. LC-MS traces for probe purity." /></div><h3><span class="label">Figure 5</span><span class="title">LC-MS traces for probe purity</span></h3></div></div><div id="ml085.s21"><h3>d. PubChem CID (corresponding to the SID)</h3><p>CID-665093</p></div><div id="ml085.s22"><h3>e. Availability from a vendor</h3><p>The probe is commercially available from InterBioScreen (ID # STOCK4S-90308).</p></div><div id="ml085.s23"><h3>f. MLS# that verifies the submission of probe molecule and five related samples that
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were submitted to the SMR collection</h3><div id="ml085.t2" class="table"><h3><span class="label">Table 2</span><span class="title">Submission information on Probe and analogs</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe/Analog</th><th id="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-# (BCCG#)</th><th id="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID</th><th id="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">SID</th><th id="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Source (vendor or BCCG syn)</th><th id="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Amt (mg)</th><th id="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Date ordered/submitted</th></tr></thead><tbody><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Probe</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0014097</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">665093</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/56373725" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">56373725</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 1</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390843</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1409759</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287589" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57287589</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 2</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390850</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400698</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287596" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57287596</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 3</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390851</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400246</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287597" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57287597</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 4</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390857</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1398345</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287604" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57287604</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr><tr><td headers="hd_h_ml085.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Analog 5</td><td headers="hd_h_ml085.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0390858</td><td headers="hd_h_ml085.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1394536</td><td headers="hd_h_ml085.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/57287605" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">57287605</a></td><td headers="hd_h_ml085.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBioScreen</td><td headers="hd_h_ml085.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">20</td><td headers="hd_h_ml085.t2_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4/15/09</td></tr></tbody></table></div></div></div><div id="ml085.s24"><h3>g. Mode of action for biological activity of probe</h3><p>The probe is a biochemical inhibitor of PLAP. The mode of action for the biological activity of this probe has not yet been elucidated.</p></div><div id="ml085.s25"><h3>h. Detailed synthetic pathway for making probe</h3><div id="ml085.fu2" class="figure"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu28.jpg" alt="Image ml085fu28" /></div></div><p>Solid 2-methoxybenzoic acid (5.0g, 32.9mmol) was transferred to a 250ml round-bottom flask and dissolved in 50 mL dry MeOH. 8 drops of c.H<sub>2</sub>SO<sub>4</sub> were added to the reaction mixture. The reaction mixture was heated at reflux for 12h. After 12 h the reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude reaction mixture was dissolved in 50 mL diethylether and washed with saturated NaHCO<sub>3</sub> (2 × 50mL) and brine solution (2 × 50mL). The organic layer was collected and the solvent was removed under reduced pressure to yield the methyl ester as a white solid (5.4 g, 99%). <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 7.82 (dd, <i>J</i> = 7.9, 1.8, 1H), 7.49 (ddd, <i>J</i> = 8.5, 7.4, 1.8, 1H), 7.00 (dtd, <i>J</i> = 4.7, 3.4, 1.0, 2H), 3.93 (s, 3H), 3.91 (s, 3H).</p><p>Methyl anisate (50.0mg, 0.3 mmol) was transferred to a glass vial and dissolved in 5 mL dry MeOH. 4-Allyl thio-semicarbazide (59.2 mg, 0.45 mmol) was added to the reaction mixture. This was followed by addition of 0.2 mL of 25%(wt) NaOMe solution. The resultant reaction mixture was heated overnight at 85<sup>o</sup>C in a sealed vial. After the reaction was complete, the solvents were evaporated under reduced pressure. The reaction mixture was cooled to 0<sup>o</sup>C and 20 mL deionized water was added to it. The pH of the reaction mixture was lowered to 5 using 10% AcOH (dropwise addition). The resultant white precipitate (4-allyl-3-(2-methoxyphenyl)-1H-1,2,4-triazole-5(4H)-thione) was filtered, dried and weighed (55mg, 74.3%). <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 7.65 – 7.47 (m, 1H), 7.35 (dd, <i>J</i> = 7.5, 1.6, 1H), 7.08 (ddd, <i>J</i> = 19.5, 13.1, 4.6, 2H), 5.75 (ddd, <i>J</i> = 16.0, 11.4, 5.7, 1H), 5.10 (d, <i>J</i> = 10.3, 1H), 4.91 (d, <i>J</i> = 17.1, 1H), 4.60 (d, <i>J</i> = 5.8, 2H), 3.86 (s, 3H). <sup>13</sup>C NMR (101 MHz, CDCl<sub>3</sub>) δ 167.79, 157.60, 150.56, 133.03, 131.79, 130.63, 120.98, 118.47, 114.67, 111.15, 55.58, 46.99.</p><p>Solid 4-allyl-3-(2-methoxyphenyl)-1H-1,2,4-triazole-5(4H)-thione (25.0 mg, 0.1mmol) was dissolved in 5 mL dry acetonitrile. 2-Chloro-3′,4′-dihydroxyacetophenone (18.8mg, 0.1mmol) was added to the reaction mixture followed by addition of Cs<sub>2</sub>CO<sub>3</sub>( 33mg, 0.1mmol). the resultant reaction mixture was stirred at room temperature for 8 hrs. The solid was filtered from the reaction mixture and the filtrate was concentrated to yield the final product 2-(4-allyl-5-(2-methoxyphenyl)-4H-1,2,4-triazol-3-ylthio)-1-(3,4-dihydroxyphenyl)ethanone (25mg, 62.5%). The product was further purified by crystallization using acetone. <sup>1</sup>H NMR (400 MHz, Acetone-D6) δ 7.54 (ddd, <i>J</i> = 8.4, 7.5, 1.8, 1H), 7.46 – 7.33 (m, 3H), 7.17 (d, <i>J</i> = 8.1, 1H), 7.07 (dt, <i>J</i> = 7.5, 0.9, 1H), 6.72 (d, <i>J</i> = 8.2, 1H), 5.89 – 5.60 (m, 1H), 5.10 (dd, <i>J</i> = 10.4, 1.1, 1H), 4.91 (dd, <i>J</i> = 17.2, 1.1, 1H), 4.78 (s, 2H), 4.49 (dd, <i>J</i> = 3.7, 1.6, 2H), 3.83 (s, 3H). <sup>13</sup>C NMR (101 MHz, Acetone-D6) δ 191.32, 159.49, 158.26, 154.41, 151.21, 148.89, 133.16, 132.97, 132.87, 124.45, 123.57, 121.53, 117.97, 117.73, 115.86, 113.80, 112.18, 55.92, 47.44, 42.01. MS (ESI) calculated C<sub>20</sub>H<sub>19</sub>N<sub>3</sub>O<sub>4</sub>S <i>m/z</i> = 397.11, found <i>m/z</i> = 398.01 [M+H].</p></div><div id="ml085.s26"><h3>i. Summary of probe properties (solubility, absorbance/fluorescence, reactivity, toxicity, etc.)</h3><p>Our internal counter screen efforts has showed CID-665093 to be inactive in two assays TNAP inhibition (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/518" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-518</a>) and G6DPH (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1020" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1020</a>), and 10-fold less active vs. IAP (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1017" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1017</a>), a very close family member of PLAP.</p><div id="ml085.s27"><h4>In Vitro Pharmacology</h4><p>Compounds CID-665093 (MLS-0014097) and CID-2102207 (MLS-0107074) were subjected to a battery of <i>in vitro</i> pharmacology assays to assess aqueous solubility, cellular permeability, plasma protein binding (PPB), plasma stability, and microsome stability. The results of these assays are presented in <a class="figpopup" href="/books/NBK47343/table/ml085.t2/?report=objectonly" target="object" rid-figpopup="figml085t2" rid-ob="figobml085t2">Table 2</a>.</p><div id="ml085.t3" class="table"><h3><span class="label">Table 3</span><span class="title">Pharmacologic Properties of MLS-01014097, MLS-0107074</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.t3_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml085.t3_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml085.t3_1_1_1_1" style="text-align:center;vertical-align:top;">Cpd-ID</th><th id="hd_h_ml085.t3_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ml085.t3_1_1_1_2" style="text-align:center;vertical-align:top;">Aqueous Solubility (μg/mL) pH 5.0/6.2/7.4 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1615" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1615</a>)</th><th id="hd_h_ml085.t3_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ml085.t3_1_1_1_3" style="text-align:center;vertical-align:top;">Permeability (×10−6 cm/s) pH 5.0/6.3/7.4 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1557" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1557</a>)</th><th id="hd_h_ml085.t3_1_1_1_4" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Plasma Protein Binding (% Bound) (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1617" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1617</a>)</th><th id="hd_h_ml085.t3_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ml085.t3_1_1_1_5" style="text-align:center;vertical-align:top;">Plasma Stability (%Remaining) Human/Mouse
|
||
(<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1591" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1591</a>/<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1592" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1592</a>)</th><th id="hd_h_ml085.t3_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_ml085.t3_1_1_1_6" style="text-align:center;vertical-align:top;">Microsomal Stability (%Remaining) Human/Mouse
|
||
(<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1555" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1555</a>/pending)</th></tr><tr><th headers="hd_h_ml085.t3_1_1_1_4" id="hd_h_ml085.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Human (10μM/1μM)</th><th headers="hd_h_ml085.t3_1_1_1_4" id="hd_h_ml085.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Mouse (10μM/1μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml085.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-665093<br /><br />MLS-0014097</td><td headers="hd_h_ml085.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.4/8.4/18.0</td><td headers="hd_h_ml085.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">90/98/58</td><td headers="hd_h_ml085.t3_1_1_1_4 hd_h_ml085.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98.6/98.7</td><td headers="hd_h_ml085.t3_1_1_1_4 hd_h_ml085.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">87.9/89.5</td><td headers="hd_h_ml085.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">100.2/83.7</td><td headers="hd_h_ml085.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">47.0/41.8</td></tr><tr><td headers="hd_h_ml085.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CID-2102207<br /><br /> MLS-0107074</td><td headers="hd_h_ml085.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.3/0.3/0.9</td><td headers="hd_h_ml085.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98/91/75*</td><td headers="hd_h_ml085.t3_1_1_1_4 hd_h_ml085.t3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">99.9/99.1</td><td headers="hd_h_ml085.t3_1_1_1_4 hd_h_ml085.t3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">99.7/99.3</td><td headers="hd_h_ml085.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">82.4/77.5</td><td headers="hd_h_ml085.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17.0/1.8</td></tr></tbody></table></div></div><p>CID-665093 (MLS-0014097) exhibits modest solubility in aqueous buffer and poor cell permeability. On the other hand, since PLAP is an extracellular enzyme, poor permeability could provide an added advantage to the probe, helping to ensure selectivity for its biological function. The compound is most soluble in aqueous buffer at pH 7.4, indicating that the compound will be sufficiently soluble for use in cellular assays conducted under normal culture conditions. CID-665093 (MLS-0014097) is extensively bound to plasma proteins in human plasma. In mouse plasma, the percent compound bound is slightly less than in human plasma. The amount of free compound available to bind the target (PLAP) is therefore greater in mice suggesting that the efficacy of this compound might be greater in mice than in humans. The compound also exhibits robust metabolic stability when exposed to both mouse and human microsome preparations.</p><p>CID-2102207 (MLS-0107074) exhibits poor solubility in aqueous buffer at all pH levels tested. In order to assess the cellular permeability, it was required that a cosolvent (20% ACN) be used in the assay to facilitate solubility. Despite the use of ACN, cellular permeability remained poor. The compound is extensively bound to plasma proteins in human and mouse plasma, and exhibits moderate stability in human and mouse plasma. CID-2102207 (MLS-0107074) was significantly metabolized in human and mouse hepatic microsomes. This suggests that the compound will be subjected to extensive first pass metabolism, limiting the use of the compound <i>in vivo</i>. Taken together these attributes indicate that this probe is best suited for biochemical experiments, but may also be used in cell based experiments when formulated with an appropriate co-solvent.</p></div></div><div id="ml085.s28"><h3>j. Properties Computed from Structure</h3><div id="ml085.tu3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.tu3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.tu3_lrgtbl__"><table><thead><tr><th id="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Property</th><th id="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:bottom;">Value</th></tr></thead><tbody><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Molecular Weight</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">397.44756 [g/mol]</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Molecular Formula</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">C<sub>20</sub>H<sub>19</sub>N<sub>3</sub>O<sub>4</sub>S</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XLogP3-AA</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">3.3</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">H-Bond Donor</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">2</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">H-Bond Acceptor</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">6</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rotatable Bond Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">8</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tautomer Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">22</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Exact Mass</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">397.109627</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MonoIsotopic Mass</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">397.109627</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Topological Polar Surface Area</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">123</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Heavy Atom Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">28</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Formal Charge</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Complexity</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">538</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Isotope Atom Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Defined Atom StereoCenter Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Undefined Atom StereoCenter Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Defined Bond StereoCenter Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Undefined Bond StereoCenter Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml085.tu3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Covalently-Bonded Unit Count</td><td headers="hd_h_ml085.tu3_1_1_1_2" rowspan="1" colspan="1" style="text-align:right;vertical-align:top;">1</td></tr></tbody></table></div></div></div></div><div id="ml085.s29"><h2 id="_ml085_s29_">4. Appendices</h2><div id="ml085.s30"><h3>a. Comparative data on (1) probe, (2) similar compound structures (establishing SAR) and (3) prior probes</h3><div id="ml085.t5" class="table"><h3><span class="label">Table 5</span><span class="title">All Purchased Analogs</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.t5_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml085.t5_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_1" style="text-align:center;vertical-align:top;">Structure</th><th id="hd_h_ml085.t5_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_2" style="text-align:center;vertical-align:top;">Cmpd ID</th><th id="hd_h_ml085.t5_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:top;">IC50(µM)</th><th id="hd_h_ml085.t5_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_4" style="text-align:center;vertical-align:top;">SID</th><th id="hd_h_ml085.t5_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_5" style="text-align:center;vertical-align:top;">CID</th><th id="hd_h_ml085.t5_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_6" style="text-align:center;vertical-align:top;">Vendor</th><th id="hd_h_ml085.t5_1_1_1_7" rowspan="2" colspan="1" headers="hd_h_ml085.t5_1_1_1_7" style="text-align:center;vertical-align:top;">VendorID</th></tr><tr><th headers="hd_h_ml085.t5_1_1_1_3" id="hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PLAP</th><th headers="hd_h_ml085.t5_1_1_1_3" id="hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">TNAP</th></tr></thead><tbody><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu29.jpg" alt="Image ml085fu29.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0014097</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.6</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373725</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">665093</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-90308</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu30.jpg" alt="Image ml085fu30.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390850</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13.6</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287596</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400698</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-91062</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu31.jpg" alt="Image ml085fu31.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390843</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.97</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287589</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1409759</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-87186</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu32.jpg" alt="Image ml085fu32.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390851</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.02</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287597</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400246</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-92693</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu33.jpg" alt="Image ml085fu33.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390858</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9.4</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287605</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1394536</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK5S-03688</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu34.jpg" alt="Image ml085fu34.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390855</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287601</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1409691</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-97188</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu35.jpg" alt="Image ml085fu35.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390857</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.45</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287604</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1398345</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-99075</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu36.jpg" alt="Image ml085fu36.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390849</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.8</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287595</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400269</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-90841</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu37.jpg" alt="Image ml085fu37.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390841</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.7</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.1</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287587</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1416608</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-84785</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu38.jpg" alt="Image ml085fu38.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0297802</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.92</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287584</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400947</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-15744</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu39.jpg" alt="Image ml085fu39.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0108835</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.53/</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40.3</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373724</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1399636</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-90782</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu40.jpg" alt="Image ml085fu40.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0101351</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.8</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287602</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3878415</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-97273</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu41.jpg" alt="Image ml085fu41.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390844</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.76</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287590</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1398070</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-88147</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu42.jpg" alt="Image ml085fu42.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390842</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.31</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287588</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1402438</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-86311</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu43.jpg" alt="Image ml085fu43.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0107074</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.87</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57309171</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2102207</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BCCG</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">PMK-14-59</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu44.jpg" alt="Image ml085fu44.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315681</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.79</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">93.4</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373578</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">838842</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5672011</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu45.jpg" alt="Image ml085fu45.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390856</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.7</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287603</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400150</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-97686</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu46.jpg" alt="Image ml085fu46.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0297827</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.9</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287583</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3735808</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK3S-98364</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu47.jpg" alt="Image ml085fu47.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315688</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.29</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.78</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373639</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1314069</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7587885</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu48.jpg" alt="Image ml085fu48.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315684</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.95</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.53</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373634</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715398</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6593203</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu49.jpg" alt="Image ml085fu49.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315686</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12.2</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">21.7</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373636</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715363</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6617586</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu50.jpg" alt="Image ml085fu50.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315685</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.78</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">10.9</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373635</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715330</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6607811</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu51.jpg" alt="Image ml085fu51.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390847</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287593</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400320</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-90030</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu52.jpg" alt="Image ml085fu52.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390853</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.22</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287599</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1400627</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-94912</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu53.jpg" alt="Image ml085fu53.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390852</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.73</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287598</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1399934</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-94867</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu54.jpg" alt="Image ml085fu54.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390854</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.59</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287600</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1401217</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-95328</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu55.jpg" alt="Image ml085fu55.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390846</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">13</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287592</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1383304</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-89768</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu56.jpg" alt="Image ml085fu56.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390839</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">25.0</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287585</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1973575</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-16633</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu57.jpg" alt="Image ml085fu57.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390840</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.63</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">40.7</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287586</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1984977</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-20993</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu58.jpg" alt="Image ml085fu58.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390848</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.94</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">19.2</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287594</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4283152</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-90562</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu59.jpg" alt="Image ml085fu59.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315690</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.58</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.58</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373641</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">946537</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7746693</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu60.jpg" alt="Image ml085fu60.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0238024</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.89</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.98</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373642</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">713665</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7764114</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu61.jpg" alt="Image ml085fu61.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0008112</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.42</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.93</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373572</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1515366</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7764254</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu62.jpg" alt="Image ml085fu62.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0255212</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.76</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.48</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373643</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2010274</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7775407</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu63.jpg" alt="Image ml085fu63.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315689</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">78.5</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373640</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1305489</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7642884</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu64.jpg" alt="Image ml085fu64.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315687</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.85</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.19</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373637</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715454</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6622859</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu65.jpg" alt="Image ml085fu65.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315680</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.56</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.71</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373577</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">720372</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5484218</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu66.jpg" alt="Image ml085fu66.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0051931</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.16</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.82</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373536</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">586278</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ChemDiv</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3294-0014</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu67.jpg" alt="Image ml085fu67.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315683</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.77</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373633</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5350662</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6588132</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu68.jpg" alt="Image ml085fu68.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315887</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.79</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.44</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373703</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4206177</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AI-204/31718048</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu69.jpg" alt="Image ml085fu69.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315886</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.06</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.15</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373702</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4450383</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AI-204/31685046</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu70.jpg" alt="Image ml085fu70.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315885</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.42</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.03</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373701</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4066568</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AI-204/31680049</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu71.jpg" alt="Image ml085fu71.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315884</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373700</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">996625</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AG-690/40754100</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu72.jpg" alt="Image ml085fu72.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315888</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373704</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">698547</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AM-807/12427007</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu73.jpg" alt="Image ml085fu73.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315883</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373696</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1223257</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AE-848/36959517</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu74.jpg" alt="Image ml085fu74.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315682</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.71</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373579</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2877377</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5933089</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu75.jpg" alt="Image ml085fu75.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315889</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373705</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">715329</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AP-048/15613011</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu76.jpg" alt="Image ml085fu76.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0080017</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>50</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373623</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">881297</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6385545</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu77.jpg" alt="Image ml085fu77.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315678</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">39.3</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373922</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2830496</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5147768</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu78.jpg" alt="Image ml085fu78.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0315679</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">18.8</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373923</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2841226</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5317936</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu79.jpg" alt="Image ml085fu79.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390862</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287609</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16415295</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK6S-42849</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu80.jpg" alt="Image ml085fu80.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390859</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.374</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.14</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287606</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5922288</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK1S-39868</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu81.jpg" alt="Image ml085fu81.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390860</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.93</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.25</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287607</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">932151</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK2S-62329</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu82.jpg" alt="Image ml085fu82.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0390861</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">15</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7.38</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">57287608</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">16000021</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK4S-15750</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu83.jpg" alt="Image ml085fu83.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0077534</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2.95</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">29.2</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373574</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2940433</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7471251</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu84.jpg" alt="Image ml085fu84.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0068603</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373638</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">805519</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Chem-Bridge</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6680720</td></tr><tr><td headers="hd_h_ml085.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><div class="graphic"><img src="/books/NBK47343/bin/ml085fu85.jpg" alt="Image ml085fu85.jpg" /></div></td><td headers="hd_h_ml085.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS-0073729</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.43</td><td headers="hd_h_ml085.t5_1_1_1_3 hd_h_ml085.t5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">>100</td><td headers="hd_h_ml085.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">56373913</td><td headers="hd_h_ml085.t5_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9551841</td><td headers="hd_h_ml085.t5_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">InterBio-Screening</td><td headers="hd_h_ml085.t5_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">STOCK2S-13283</td></tr></tbody></table></div></div></div><div id="ml085.s31"><h3>b. Comparative data showing probe specificity for target</h3><div id="ml085.t4" class="table"><h3><span class="label">Table 4</span><span class="title">SAR and Selectivity</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47343/table/ml085.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml085.t4_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Compound ID</th><th id="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay Format</th><th id="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay Target</th><th id="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">No of Runs</th><th id="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">IC<sub>50</sub> Value (μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Luminescent</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">TNAP</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">4</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">>100</td></tr><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Luminescent</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">PLAP</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">~ 6</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2.34</td></tr><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Luminescent</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">IAP</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">20.7</td></tr><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Colorimetric</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">GAPDH</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">2</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">>100</td></tr><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">FP</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">BCL-b/TR3</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">>100</td></tr><tr><td headers="hd_h_ml085.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">MLS-0014097</td><td headers="hd_h_ml085.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">FP</td><td headers="hd_h_ml085.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Bfl-1</td><td headers="hd_h_ml085.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">1</td><td headers="hd_h_ml085.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">>100</td></tr></tbody></table></div></div></div></div><div id="ml085.s32"><h2 id="_ml085_s32_">5. Bibliography</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="ml085.r1">Hoylaerts MF, Manes T, Millán JL. Molecular mechanism of uncompetitive inhibition of human placental and germ-cell alkaline phosphatase. <span><span class="ref-journal">Biochem J. </span>1992;<span class="ref-vol">286</span>(Pt 1):23–30.</span> [<a href="/pmc/articles/PMC1133013/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1133013</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1520273" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1520273</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="ml085.r2">Wennberg C, Kozlenkov A, Di Mauro S, Fröhlander N, Beckman L, Hoylaerts MF, Millán JL. Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP). <span><span class="ref-journal">Human Mutation. </span>2002;<span class="ref-vol">19</span>(3):258–267.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11857742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11857742</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="ml085.r3">Wahren B 1, Hinkula J, Stigbrand T, Jeppsson A, Andersson L, Esposti PL, Edsmyr F, Millán JL. Phenotypes of placental-type alkaline phosphatase in seminoma sera. <span><span class="ref-journal">Int J of Cancer. </span>2006;<span class="ref-vol">37</span>(4):595–600.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3957465" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3957465</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="ml085.r4">Fishman WH. Clinical and biological significance of an isozyme tumor marker—PLAP. <span><span class="ref-journal">Clin Biochem. </span>1987;<span class="ref-vol">20</span>:387–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3325192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3325192</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK47343</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/21433359" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">21433359</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml086/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml084/" title="Next page in this title">Next ></a></div></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/NBK47343/?report=reader">PubReader</a></li><li><a href="/books/NBK47343/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK47343" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK47343" style="display:none" title="Cite this Page"><div class="bk_tt">Sergienko E, Garcia X, Brown B, et al. Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1. 2009 Apr 18 [Updated 2010 Sep 2]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK47343/pdf/Bookshelf_NBK47343.pdf">PDF version of this page</a> (571K)</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="#ml085.s2" ref="log$=inpage&link_id=inpage">Probe Structure & Characteristics</a></li><li><a href="#ml085.s3" ref="log$=inpage&link_id=inpage">Recommendations for the scientific use of this probe</a></li><li><a href="#ml085.s4" ref="log$=inpage&link_id=inpage">Scientific Rationale for Project</a></li><li><a href="#ml085.s5" ref="log$=inpage&link_id=inpage">Project Description</a></li><li><a href="#ml085.s17" ref="log$=inpage&link_id=inpage">Probe</a></li><li><a href="#ml085.s29" ref="log$=inpage&link_id=inpage">Appendices</a></li><li><a href="#ml085.s32" ref="log$=inpage&link_id=inpage">Bibliography</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=2358778" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" 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