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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7) - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="Probe Reports from the NIH Molecular Libraries Program [Internet]">
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<meta name="citation_title" content="Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7)">
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<meta name="citation_publisher" content="National Center for Biotechnology Information (US)">
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<meta name="citation_date" content="2010">
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<meta name="citation_author" content="Miguel Guerrero">
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<meta name="citation_author" content="Mariangela Urbano">
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<meta name="citation_author" content="Zhiwei Wang">
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<meta name="citation_author" content="Jian Zhao">
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<meta name="citation_author" content="Subash Velaparthi">
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<meta name="citation_author" content="Marie-Therese Schaeffer">
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<meta name="citation_author" content="Steven J Brown">
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<meta name="citation_author" content="S Adrian Saldanha">
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<meta name="citation_author" content="Peter Chase">
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<meta name="citation_author" content="Jill Ferguson">
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<meta name="citation_author" content="Peter Hodder">
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<meta name="citation_author" content="Hugh Rosen">
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<meta name="citation_author" content="Olivier Civelli">
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<meta name="citation_author" content="Edward Roberts">
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<meta name="citation_pmid" content="23762933">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK143551/">
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<meta name="DC.Title" content="Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7)">
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<meta name="DC.Type" content="Text">
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<meta name="DC.Publisher" content="National Center for Biotechnology Information (US)">
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<meta name="DC.Contributor" content="Miguel Guerrero">
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<meta name="DC.Contributor" content="Mariangela Urbano">
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<meta name="DC.Contributor" content="Zhiwei Wang">
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<meta name="DC.Contributor" content="Jian Zhao">
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<meta name="DC.Contributor" content="Subash Velaparthi">
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<meta name="DC.Contributor" content="Marie-Therese Schaeffer">
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<meta name="DC.Contributor" content="Steven J Brown">
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<meta name="DC.Contributor" content="S Adrian Saldanha">
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<meta name="DC.Contributor" content="Peter Chase">
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<meta name="DC.Contributor" content="Jill Ferguson">
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<meta name="DC.Contributor" content="Peter Hodder">
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<meta name="DC.Contributor" content="Hugh Rosen">
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<meta name="DC.Contributor" content="Olivier Civelli">
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<meta name="DC.Contributor" content="Edward Roberts">
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<meta name="DC.Date" content="2010">
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<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK143551/">
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<meta name="description" content="Heterotrimeric G-protein coupled receptors (GPCRs), the largest family of membrane-bound receptors, are major targets for therapeutic applications due to their broad tissue distribution, structural diversity, varied modes of action, and disease-associated mutations. The recently de-orphanized GPCR GPR7 is distributed predominantly in the central nervous system. Neuropeptides W (NPW) and B (NPB) have been identified as endogenous ligands of GPR7. GPR7 represents a new and expanding target for drug development as it has been demonstrated to modulate the release of pituitary-derived hormones and implicated in feeding behavior, the development of obesity, and mediating the inflammatory pain response. There is a significant medical need for novel compounds for treating chronic pain that are effective, long lasting, and safe. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a potent and selective GPR7 antagonist probe, ML250, by high-throughput screening using a cell-based fluorescence assay. ML250 inhibits human GPR7 expression in the presence of a GPR7 agonist NPW with an IC50 of 124nM–244nM. In a counterscreen for melanin-concentrating hormone receptor 1 (MCH1) antagonism in the presence of an agonist, ML250 has an IC50 of >20 μM, resulting in a selectivity for GPR7 of 82 – >161 fold. ML250 is nontoxic to U2OS cells, with a CC50 of > 20 μM. We previously reported ML181, a 272 nM antagonist probe that is 14-fold selective for GPR7 over MCH1, and the first reported small molecule modulator of GPR7. ML250 has comparable potency but greater selectivity than ML181 and will be a valuable tool in elucidating the diverse roles of this receptor in physiological and pathological processes. ML250 also represents a potential therapeutic option in treating chronic pain.">
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<meta name="og:description" content="Heterotrimeric G-protein coupled receptors (GPCRs), the largest family of membrane-bound receptors, are major targets for therapeutic applications due to their broad tissue distribution, structural diversity, varied modes of action, and disease-associated mutations. The recently de-orphanized GPCR GPR7 is distributed predominantly in the central nervous system. Neuropeptides W (NPW) and B (NPB) have been identified as endogenous ligands of GPR7. GPR7 represents a new and expanding target for drug development as it has been demonstrated to modulate the release of pituitary-derived hormones and implicated in feeding behavior, the development of obesity, and mediating the inflammatory pain response. There is a significant medical need for novel compounds for treating chronic pain that are effective, long lasting, and safe. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a potent and selective GPR7 antagonist probe, ML250, by high-throughput screening using a cell-based fluorescence assay. ML250 inhibits human GPR7 expression in the presence of a GPR7 agonist NPW with an IC50 of 124nM–244nM. In a counterscreen for melanin-concentrating hormone receptor 1 (MCH1) antagonism in the presence of an agonist, ML250 has an IC50 of >20 μM, resulting in a selectivity for GPR7 of 82 – >161 fold. ML250 is nontoxic to U2OS cells, with a CC50 of > 20 μM. We previously reported ML181, a 272 nM antagonist probe that is 14-fold selective for GPR7 over MCH1, and the first reported small molecule modulator of GPR7. ML250 has comparable potency but greater selectivity than ML181 and will be a valuable tool in elucidating the diverse roles of this receptor in physiological and pathological processes. ML250 also represents a potential therapeutic option in treating chronic pain.">
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id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK143551_"><span class="title" itemprop="name">Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7)</span></h1><p class="contribs">Guerrero M, Urbano M, Wang Z, et al.</p><p class="fm-aai"><a href="#_NBK143551_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p>Heterotrimeric G-protein coupled receptors (GPCRs), the largest family of membrane-bound receptors, are major targets for therapeutic applications due to their broad tissue distribution, structural diversity, varied modes of action, and disease-associated mutations. The recently de-orphanized GPCR GPR7 is distributed predominantly in the central nervous system. Neuropeptides W (NPW) and B (NPB) have been identified as endogenous ligands of GPR7. GPR7 represents a new and expanding target for drug development as it has been demonstrated to modulate the release of pituitary-derived hormones and implicated in feeding behavior, the development of obesity, and mediating the inflammatory pain response. There is a significant medical need for novel compounds for treating chronic pain that are effective, long lasting, and safe. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a potent and selective GPR7 antagonist probe, <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a>, by high-throughput screening using a cell-based fluorescence assay. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> inhibits human GPR7 expression in the presence of a GPR7 agonist NPW with an IC50 of 124nM–244nM. In a counterscreen for melanin-concentrating hormone receptor 1 (MCH1) antagonism in the presence of an agonist, <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> has an IC50 of >20 μM, resulting in a selectivity for GPR7 of 82 – >161 fold. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is nontoxic to U2OS cells, with a CC50 of > 20 μM. We previously reported <a href="/pcsubstance/?term=ML181[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML181</a>, a 272 nM antagonist probe that is 14-fold selective for GPR7 over MCH1, and the first reported small molecule modulator of GPR7. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> has comparable potency but greater selectivity than <a href="/pcsubstance/?term=ML181[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML181</a> and will be a valuable tool in elucidating the diverse roles of this receptor in physiological and pathological processes. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=abstract&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> also represents a potential therapeutic option in treating chronic pain.</p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> 1-R03-DA026557-01</p><p><b>Screening Center Name & PI:</b> The Scripps Research Institute Molecular Screening Center (SRIMSC), H Rosen</p><p><b>Chemistry Center Name & PI:</b> SRIMSC, H Rosen</p><p><b>Assay Submitter & Institution:</b> Olivier Civelli, University of California Irvine</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1880" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1880</a></p><div id="ml250.s1"><h2 id="_ml250_s1_">Probe Structure & Characteristics</h2><div id="ml250.fu1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK143551/bin/ml250fu1.jpg" alt="ML250." /></div><h3><span class="title">ML250</span></h3></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250tu1"><a href="/books/NBK143551/table/ml250.tu1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml250tu1" rid-ob="figobml250tu1"><img class="small-thumb" src="/books/NBK143551/table/ml250.tu1/?report=thumb" src-large="/books/NBK143551/table/ml250.tu1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml250.tu1"><a href="/books/NBK143551/table/ml250.tu1/?report=objectonly" target="object" rid-ob="figobml250tu1">Table</a></h4></div></div></div><div id="ml250.s2"><h2 id="_ml250_s2_">Recommendations for Scientific Use of the Probe</h2><p>Heterotrimeric G-protein coupled receptors (GPCRs), the largest family of membrane-bound receptors, are major targets for therapeutic applications due to their broad tissue distribution, structural diversity, varied modes of action, and disease-associated mutations (<a class="bibr" href="#ml250.r1" rid="ml250.r1">1</a>–<a class="bibr" href="#ml250.r4" rid="ml250.r4">4</a>). The recently de-orphanized GPCR GPR7 (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>) is distributed predominantly in the central nervous system (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>–<a class="bibr" href="#ml250.r6" rid="ml250.r6">6</a>). Neuropeptides W (NPW) and B (NPB) have been identified as endogenous ligands of GPR7 (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>, <a class="bibr" href="#ml250.r7" rid="ml250.r7">7</a>). GPR7 represents a new and expanding target for drug development as it has been demonstrated to modulate the release of pituitary-derived hormones, been implicated in feeding behavior, the development of obesity, and mediating the inflammatory pain response (<a class="bibr" href="#ml250.r8" rid="ml250.r8">8</a>–<a class="bibr" href="#ml250.r10" rid="ml250.r10">10</a>). The probe compound <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> reported here inhibits NPW activation of GPR7 receptor with an IC50 in the low nanomolar range, and displays high selectivity <i>versus</i> melanin-concentrating hormone receptor 1 (MCH1) receptor. This probe represents a significant milestone that will allow experiments aimed to elucidate the diverse roles of this receptor in physiological and pathological processes. This probe also represents a potential therapeutic option for treating chronic pain. There is a significant medical need for novel compounds for treating chronic pain that are effective, long lasting, and safe (<a class="bibr" href="#ml250.r11" rid="ml250.r11">11</a>).</p></div><div id="ml250.s3"><h2 id="_ml250_s3_">1. Introduction</h2><p>Heterotrimeric G-protein coupled receptors (GPCRs) are the largest family of membrane-bound receptors and major targets for therapeutic applications due in part to their broad tissue distribution, structural diversity, varied modes of action, and disease-associated mutations (<a class="bibr" href="#ml250.r1" rid="ml250.r1">1</a>–<a class="bibr" href="#ml250.r4" rid="ml250.r4">4</a>). In particular, GPCRs are widely distributed in the peripheral and central nervous systems where they are located on the plasma membrane of neurons along the nociceptive pathways (<a class="bibr" href="#ml250.r3" rid="ml250.r3">3</a>, <a class="bibr" href="#ml250.r12" rid="ml250.r12">12</a>). They have been shown to play an important role in the modulation of pain and are one of the most important therapeutic targets in the area of pain management (<a class="bibr" href="#ml250.r3" rid="ml250.r3">3</a>, <a class="bibr" href="#ml250.r13" rid="ml250.r13">13</a>). Chronic pain is a debilitating condition that exerts a high social cost in terms of productivity, economic impact, and quality of life (<a class="bibr" href="#ml250.r14" rid="ml250.r14">14</a>–<a class="bibr" href="#ml250.r16" rid="ml250.r16">16</a>). Currently available therapies yield limited success in treating such pain, suggesting the need for new insight into underlying mechanisms (<a class="bibr" href="#ml250.r11" rid="ml250.r11">11</a>).</p><p>The recently de-orphanized GPCR GPR7 (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>) represents a new and expanding target for drug development as it has been demonstrated to modulate the release of pituitary-derived hormones, regulate feeding behavior, and manipulate pain pathways (<a class="bibr" href="#ml250.r17" rid="ml250.r17">17</a>). The genes for GPR7 and the closely related GPR8 receptor share 70% sequence identity with each other, and significant similarities with the transmembrane regions of the opioid and somatostatin receptors (<a class="bibr" href="#ml250.r18" rid="ml250.r18">18</a>). Several studies have shown that GPR7 is distributed predominantly in the central nervous system, with the highest expression found in the hippocampus and amygdale (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>, <a class="bibr" href="#ml250.r12" rid="ml250.r12">12</a>, <a class="bibr" href="#ml250.r17" rid="ml250.r17">17</a>–<a class="bibr" href="#ml250.r18" rid="ml250.r18">18</a>). Studies identifying the energy-regulating Neuropeptide W (NPW) and Neuropeptide B (NPB) as endogenous ligands of GPR7 (<a class="bibr" href="#ml250.r5" rid="ml250.r5">5</a>–<a class="bibr" href="#ml250.r7" rid="ml250.r7">7</a>, <a class="bibr" href="#ml250.r19" rid="ml250.r19">19</a>) that bind to GPR7 and GPR8 with similar affinity (<a class="bibr" href="#ml250.r19" rid="ml250.r19">19</a>), and the development of abnormally increased appetite and obesity in male GPR7 knockout mice (<a class="bibr" href="#ml250.r8" rid="ml250.r8">8</a>), implicate GPR7 in feeding behavior.</p><p>Most notably, while under normal conditions GPR7 is expressed at low levels in the spinal cord; its expression is dramatically increased in patients suffering from inflammatory/immune-mediated neuropathies (<a class="bibr" href="#ml250.r10" rid="ml250.r10">10</a>). Similar results have been found in animal models using immune-inflammatory- and ligation-induced nerve injuries (<a class="bibr" href="#ml250.r9" rid="ml250.r9">9</a>, <a class="bibr" href="#ml250.r20" rid="ml250.r20">20</a>). NPB-deficient mice demonstrate a super sensitivity in response to inflammatory pain, directly linking the NPB/GPR7 system to pain sensation (<a class="bibr" href="#ml250.r9" rid="ml250.r9">9</a>). Therefore, understanding the role of GPR7 and its cognate ligands NPB and NPW may provide new physiological insights and may offer novel targets for therapeutic drug development (<a class="bibr" href="#ml250.r17" rid="ml250.r17">17</a>).</p><p>The aim of this project is to identify small molecule potent and selective GPR7 antagonists to be used as valuable basic research tools that will greatly facilitate understanding the involvement of GPR7 in chronic pain, its role in the mechanism of pain transmission, and its interaction with other pain-related pathways. In particular, small compounds will be useful to study GPR7 with regard to its role in inflammatory neuropathies where established animal models are available.</p><p>We previously reported probe <a href="/pcsubstance/?term=ML181[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML181</a> (<a class="figpopup" href="/books/NBK143551/table/ml250.t1/?report=objectonly" target="object" rid-figpopup="figml250t1" rid-ob="figobml250t1">Table 1</a>), a 272 nM antagonist that is 14-fold selective for GPR7 over the antitarget MCH1, and the first reported small molecule modulator of GPR7 (<a class="bibr" href="#ml250.r21" rid="ml250.r21">21</a>). A search of patents posted on the US Patent and Trademark Office website on August 25, 2011, returned no results for GPR7-specific inhibitors or antagonists, and a PubMed search on the same date found no GPR7-specific inhibitors or antagonists.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250t1"><a href="/books/NBK143551/table/ml250.t1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figml250t1" rid-ob="figobml250t1"><img class="small-thumb" src="/books/NBK143551/table/ml250.t1/?report=thumb" src-large="/books/NBK143551/table/ml250.t1/?report=previmg" alt="Table 1. Published GPR7 antagonist." /></a><div class="icnblk_cntnt"><h4 id="ml250.t1"><a href="/books/NBK143551/table/ml250.t1/?report=objectonly" target="object" rid-ob="figobml250t1">Table 1</a></h4><p class="float-caption no_bottom_margin">Published GPR7 antagonist. </p></div></div></div><div id="ml250.s4"><h2 id="_ml250_s4_">2. Materials and Methods</h2><p>The following cell lines were provided by the Assay Provider: hGPR7 HEK293T/Gqi3, hMCHR1 HEK293T/Gqi3, and U2OS. The following reagents were obtained from Invitrogen: DMEM (11965), Hank’s Balanced Salt Solution (14025-092), Geneticin (10131-027), Hygromycin-B (10687-010), Trypsin-EDTA solution (25200-056), 100X Penicillin-Streptomycin-Neomycin mix (15640-055), Zeocin (46-0509), and Fetal Bovine Serum (16140-071). Fluo-8 No Wash Calcium Assay Kit (36316) and Trypan red plus (2456) were obtained from ABD Bioquest. Fetal Bovine Serum (FB-02) was obtained from Omega Scientific. T-175 tissue culture flasks (431080), 150 mm tissue culture dishes (430599), and 384-well plates (3570) were obtained from Corning. 1536-well plates (19326) were obtained from Aurora. Neuropeptide W-23 NPW-23) (Human) (61653) was obtained from AnaSpec. Melanin-Concentrating Hormone (MCH) (Human, Mouse, Rat) (070-47), Neuropeptide W-23 (NPW-23)/L8 (Human) (005-60), and Neuropeptide B-23 (NPB-23)/L8 (Human) (005-53) were obtained from Phoenix Pharmaceuticals. T-75 tissue culture flasks (178905) were obtained from Nunc. 384-well plates (781964) were obtained from Greiner. Rotenone (R8875) and DMSO (472301) were obtained from Sigma. CellTiter Glo (S-G7570) was obtained from Promega. 96-well plates (T-3073-46) were obtained from ISC BioExpress. Reagents for the Ricerca HitProfilingScreen + CYP450 assay were provided by Ricerca Biosciences, LLC.</p><div id="ml250.s5"><h3>2.1. Assays</h3><div id="ml250.s6"><h4>LC-MS/MS</h4><p>All analytical methods are in MRM mode where the parent ion is selected in Q1 of the mass spectrometer. The parent ion is fragmented and a characteristic fragment ion is monitored in Q3. MRM mass spectroscopy methods are particularly sensitive because additional time is spent monitoring the desired ions and not sweeping a large mass range. Methods will be rapidly set up using Automaton<sup>®</sup> (Applied Biosystems), where the compounds are listed with their name and mass in an Excel datasheet. Compounds are submitted in a 96-well plate to the HPLC autosampler and are slowly injected without a column present. A narrow range centered on the indicated mass is scanned to detect the parent ion. The software then evaluates a few pre-selected parameters to determine conditions that maximize the signal for the parent ion. The molecule is then fragmented in the collision cell of the mass spectrometer and fragments with m/z larger than 70 but smaller than the parent mass are determined. Three separate collision energies are evaluated to fragment the parent ion and the largest three ions are selected. Each of these three fragment ions is further optimized and the best fragment is chosen. The software then inserts the optimized masses and parameters into a template method and saves it with a unique name that indicates the individual compound being optimized. Spectra for the parent ion and the fragmentation pattern are saved and can be reviewed later.</p></div><div id="ml250.s7"><h4>Solubility</h4><p>The solubility of compounds was tested in phosphate buffered saline, pH 7.4. Compounds were inverted for 24 hours in test tubes containing 1–2 mg of compound with 1 mL of PBS. The samples were centrifuged and analyzed by HPLC (Agilent 1100 with diode-array detector). Peak area was compared to a standard of known concentration. In cases when the concentration was too low for UV analysis or when the compound did not possess a good chromophore, LC-MS/MS analysis was used.</p></div><div id="ml250.s8"><h4>Stability</h4><p>Demonstration of stability in PBS was conducted under conditions likely to be experienced in a laboratory setting. The compound was dissolved in 1 mL of PBS at a concentration of 10 μM, unless its maximum solubility was insufficient to achieve this concentration. Low solubility compounds were tested between ten and fifty percent of their solubility limit. The solution was immediately aliquoted into seven standard polypropylene microcentrifuge tubes which were stored at ambient temperature in a block microcentrifuge tube holder. Individual tubes were frozen at -80 °C at 0, 1, 2, 4, 8, 24, and 48 hours. The frozen samples were thawed in a room temperature and an equal volume of acetonitrile was added prior to determination of concentration by LC-MS/MS.</p></div><div id="ml250.s9"><h4>Determination of glutathione reactivity</h4><p>One μL of a 10 mM compound stock solution was added to 1 mL of a freshly prepared solution of 50 μM reduced glutathione. Final compound concentration is 10 μM unless solubility limited. The solution was allowed to incubate at 37°C for two hours prior to being directly analyzed for glutathione adduct formation. LC-MS/MS analysis of GSH adducts was performed on an API 4000 Q-TrapTM mass spectrometer equipped with a Turboionspray source (Applied Biosystems, Foster City, CA). Two methodologies were utilized—a negative precursor ion (PI) scan of m/z 272, corresponding to GSH fragmenting at the thioether bond, and a neutral loss scan of -129 AMU to detect GSH adducts. This triggered positive ion enhanced resolution and enhanced product ion scans (<a class="bibr" href="#ml250.r22" rid="ml250.r22">22</a>–<a class="bibr" href="#ml250.r23" rid="ml250.r23">23</a>).</p></div><div id="ml250.s10"><h4>Primary uHTS assay to identify GPR7 antagonists (AID 1861, AID 1952, and AID 2251)</h4><p><b>Assay Overview:</b> The purpose of this assay was to identify compounds that inhibit GPR7 activity. Although GPR7 is naturally coupled to Gαi, which decreases cAMP levels upon activation, this assay employs a chimeric cell line that forces the receptor to use Gqi3, and therefore the assay readout is calcium release. In this assay, HEK cells stably co-transfected with the human GPR7 receptor and Gqi3 (hGPR7 HEK293T/Gqi3 cell line) were treated with test compounds, followed by measurement of intracellular calcium as monitored by the FLUO-8 fluorescent, cell permeable calcium indicator dye. As designed, compounds that act as GPR7 antagonists will decrease calcium mobilization, resulting in decreased relative fluorescence of the indicator dye, and thus decreased well fluorescence. Test compounds were assayed in singlicate at a final nominal concentration of 4.4 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>), in triplicate at a final nominal concentration of 4.4 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>), or in triplicate in a 10-point 1:3 dilution series starting at a nominal test concentration of 44 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2251</a>).</p><p><b>Protocol Summary:</b> The hGPR7 HEK293T/Gqi3 cell line was routinely cultured in T-175 sq cm flasks at 37°C and 95% relative humidity (RH). The growth media consisted of Dulbecco’s Modified Eagle’s Media (DMEM) supplemented with 10% v/v heat-inactivated qualified fetal bovine serum, 25 mM HEPES, 200 ug/mL Hygromycin-B, 200 ug/mL Geneticin, 0.625 ug/mL Puromycin, and 1X antibiotic mix (penicillin, streptomycin, and neomycin). The day before the assay 1.5 × 10<sup>3</sup> cells in 3 μL of growth media were seeded into each well of 1536 well microtiter plates and allowed to incubate at 37°C, 5% CO<sub>2</sub>, and 95 % RH for 23 hours. Next, 2 μL of the fluorogenic Fluo-8 intracellular calcium indicator mixture with 1 mM trypan red plus (prepared according to the manufacturer’s protocol) was added to each well. After incubation for 1 hour at 37°C, 5% CO<sub>2</sub>, and 95 % RH, 22 nL of test compound in DMSO, or DMSO alone, were dispensed to the appropriate wells. The assay was started after a 30-minute incubation at room temperature by performing a basal read of plate fluorescence (470–495 nm excitation and 515–575 nm emission) for 5 seconds on the FLIPR Tetra (Molecular Devices). Next, 15 nL of GPR7 agonist NPW (2 nM final concentration) in DMSO, or DMSO alone, were dispensed to the appropriate wells. Then a real-time fluorescence measurement was immediately performed for the remaining 180 seconds of the assay. <b>Assay Cutoff:</b> 1) Plate-based cutoff (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>); 2) Compounds that inhibited GPR7 greater than 23.76% were considered active (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>); 3) Compounds with an IC50 < 10 μM were considered active.</p></div><div id="ml250.s11"><h4>Counterscreen uHTS assay to identify MCH1 antagonists (AID 2148 and AID 2257)</h4><p><b>Assay Overview:</b> The purpose of this assay was to identify compounds that inhibit the melanin-concentrating hormone receptor 1 (MCH1) (GPR24), the receptor for MCH, a cyclic hypothalamic neuropeptide that promotes food intake (17), increases leptin and insulin release (18), and modulates energy metabolism (19). This assay also serves as a counterscreen for compounds identified as active in a previous set of experiments entitled, “Fluorescence-based primary cell-based high throughput screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)” (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>), and that confirmed activity in a previous set of experiments entitled, “Fluorescence-based confirmation cell-based high throughput screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)” (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>). This assay employs HEK cells stably co-transfected with human MCH1 and a chimeric Gαqi3. Cells are treated with test compounds followed by measurement of intracellular calcium as monitored by the FLUO-8 fluorescent, cell permeable calcium indicator dye. As designed, compounds that act as human MCH1 antagonists will decrease calcium mobilization, resulting in decreased relative fluorescence of the indicator dye, and thus decreased well fluorescence. Test compounds were assayed in triplicate at a final nominal concentration of 4.4 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a>) or in triplicate in a 10-point 1:3 dilution series starting at a nominal test concentration of 44 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2257</a>).</p><p><b>Protocol Summary:</b> The hMCHR1 HEK293T/Gqi3 cell line was routinely cultured in T-175 sq cm flasks at 37°C and 95% RH. The growth media consisted of DMEM supplemented with 10% v/v heat-inactivated qualified fetal bovine serum, 25 mM HEPES, 200 ug/mL Hygromycin-B, 100 ug/mL Zeocin, 200 ug/mL Geneticin and 1X antibiotic mix (penicillin, streptomycin, and neomycin). The day before the assay, 1.5 × 10<sup>3</sup> cells in 3 μL of growth media were seeded into each well of 1536 well microtiter plates and allowed to incubate at 37°C, 5% CO<sub>2</sub>, and 95 % RH for 23 hours. Next, 2 μL of the fluorogenic Fluo-8 intracellular calcium indicator mixture with 1 mM trypan red plus (prepared according to the manufacturer’s protocol) was added to each well. After incubation for 1 hour at 37°C, 5% CO<sub>2</sub>, and 95 % RH, 22 nL of test compound in DMSO, or DMSO alone, were dispensed to the appropriate wells. The assay was started after an additional 30-minute incubation at room temperature by performing a basal read of plate fluorescence (470–495 nm excitation and 515–575 nm emission) for 5 seconds on the FLIPR Tetra (Molecular Devices). Next, 15 nL of MCH peptide agonist (0.2 nM final concentration) in DMSO, or DMSO alone, were dispensed to the appropriate wells. Then a real-time fluorescence measurement was immediately performed for the remaining 180 seconds of the assay. <b>Assay Cutoff:</b> 1) Compounds that inhibited MCH1 greater than 21.36% were considered active (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a>); 2) Compounds with an IC50 ≤ 10 μM were considered active.</p></div><div id="ml250.s12"><h4>Late-stage assay to identify GPR7 antagonists (AID 504868 and AID 540365)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine dose response curves for synthesized compounds in a 384-well plate format for antagonism of GPR7. The assay was as described above for the uHTS assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>, and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2251</a>). Test compounds were assayed in triplicate in an 8-point 1:3 dilution series starting at a nominal test concentration of 20 μM.</p><p><b>Protocol Summary:</b> The hGPR7 HEK293T/Gqi3 cell line was routinely cultured in T-75 sq cm flasks at 37°C and 95% RH. The growth media consisted of DMEM supplemented with 10% v/v heat-inactivated qualified fetal bovine serum, 25 mM HEPES, 200 ug/mL Hygromycin-B, 200 ug/mL Geneticin, 0.625 ug/mL Puromycin, and 1X antibiotic mix (penicillin, streptomycin, and neomycin). The day before the assay 1 × 10<sup>4</sup> cells in 25 μL of growth media were seeded into each well of 384 well microtiter plates and allowed to incubate at 37°C, 5% CO<sub>2</sub>, and 95 % RH for 23 hours. Next, 25 μL of the fluorogenic Fluo-8 intracellular calcium indicator mixture with 1 mM trypan red plus (prepared according to the manufacturer’s protocol) was added to each well. After incubation for 50 minutes at 37°C, 5% CO<sub>2</sub>, and 95 % RH, 100 nL of test compound in DMSO, or DMSO alone, were dispensed to the appropriate wells. The assay was started after an additional 15-minute incubation at room temperature by performing a basal read of plate fluorescence (470–495 nm excitation and 515–575 nm emission) for 5 seconds on the FLIPR Tetra (Molecular Devices). Next, 5.5 nL of GPR7 agonist (20 nM final concentration) in FLIPR buffer (HBSS/20 mM Hepes/0.1% BSA) was dispensed to the appropriate wells. Then a real time fluorescence measurement was immediately performed for the remaining 180 seconds of the assay. <b>Assay Cutoff:</b> Compounds with an IC50 ≤ 10 μM were considered active.</p></div><div id="ml250.s13"><h4>Late-stage counterscreen assay to identify MCH1 antagonists (AID 504889 and AID 540371)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine dose response for a set of synthesized compounds in a 384-well format counterscreen assay for antagonism of MCH1. The assay was as described above for the uHTS assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2257</a>). Test compounds were assayed in triplicate in an 8-point 1:3 dilution series starting at a nominal test concentration of 20 μM.</p><p><b>Protocol Summary:</b> The hMCHR1 HEK293T/Gqi3 cell line was routinely cultured in T-75 sq cm flasks at 37°C and 95% RH. The growth media consisted of DMEM supplemented with 10% v/v heat-inactivated qualified fetal bovine serum, 25 mM HEPES, 200 ug/mL Hygromycin-B, 100 ug/mL Zeocin, 200 ug/mL Geneticin and 1X antibiotic mix (penicillin, streptomycin, and neomycin). The day before the assay, 1 × 10<sup>4</sup> cells in 3 μL of growth media were seeded into each well of 384 well microtiter plates and allowed to incubate at 37°C, 5% CO<sub>2</sub>, and 95 % RH for 23 hours. Next, 25 μL of the fluorogenic Fluo-8 intracellular calcium indicator mixture with 1 mM trypan red plus (prepared according to the manufacturer’s protocol) was added to each well. After incubation for 50 minutes at 37°C, 5% CO<sub>2</sub>, and 95 % RH, 100 nL of test compound in DMSO, or DMSO alone, were dispensed to the appropriate wells. The assay was started after an additional 15-minute incubation at room temperature by performing a basal read of plate fluorescence (470–495 nm excitation and 515–575 nm emission) for 5 seconds on the FLIPR Tetra (Molecular Devices). Next, 5.5 nL of MCH peptide agonist (30 nM final concentration) in FLIPR buffer (HBSS/20 mM Hepes/0.1% BSA) were dispensed to the appropriate wells. Then a real time fluorescence measurement was immediately performed for the remaining 180 seconds of the assay. <b>Assay Cutoff:</b> Compounds with an IC50 ≤ 10 μM were considered active.</p></div><div id="ml250.s14"><h4>Cytotoxicity assay (AID 504886 and AID 588326)</h4><p><b>Assay Overview:</b> The purpose of this assay was to determine cytotoxicity of a powder sample of a compound identified as active in the late-stage assay to identify GPR7 antagonists (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463251</a>). In this assay, U2OS cells were incubated with test compound, followed by determination of cell viability. The assay utilizes the CellTiter-Glo luminescent reagent to measure intracellular ATP in viable cells. Luciferase present in the reagent catalyzes the oxidation of beetle luciferin to oxyluciferin and light in the presence of cellular ATP. Well luminescence is directly proportional to ATP levels and cell viability. As designed, compounds that reduce cell viability will reduce ATP levels, luciferin oxidation and light production, resulting in decreased well luminescence. Compounds were tested in sextuplet in a 7-point 1:3 dilution series starting at a nominal test concentration of 20 micromolar.</p><p><b>Protocol Summary:</b> U2OS cells were grown in DMEM supplemented with 10% v/v fetal bovine serum, 2 mM L-Glutamine, and 100U/mL penicillin and streptomycin. Prior to the start of the assay, 2 × 10<sup>5</sup> U2OS cells in 20 μL HBSS were dispensed into wells of a 384-well tissue culture-treated microtiter plate. Test compound was diluted 1:100 in growth medium (100 μM final concentration) and then serially diluted 1:3 in growth medium. The assay was started immediately by dispensing 5 μL of test compound, media alone, or rotenone as a positive control (150 μM final concentration) to the appropriate wells. The plates were then incubated for 2 hours at 37°C. The plate was then equilibrated at room temperature for 30 minutes. The assay was stopped by dispensing 25 μL of CellTiter-Glo reagent to each well followed by incubation in the dark at room temperature for 10 minutes. Well luminescence was measured on the ViewLux plate reader. <b>Activity Cutoff:</b> Compounds with a CC50 value of ≤ 10 μM were considered active (cytotoxic).</p></div><div id="ml250.s15"><h4>Ricerca HitProfilingScreen + CYP450 panel assay (AID 540345)</h4><p><b>Assay Overview:</b> The purpose of this panel of binding assays performed by Ricerca Biosciences, LLC, was to identify a subset of potential receptors, transporters, ion channels, etc. for which the GPR7 antagonist compound CID 46172919 displays affinity.</p><p><b>Protocol Summary:</b> Assays for CYP450, 1A2; CYP450, 2C19; CYP450, 2C9; CYP450, 2D6; and CYP450, 3A4 were enzyme assays using human recombinant insect Sf9 cells with 5 μM 3-cyano-7-ethoxycoumarin as substrate (except for CYP450, 3A4, which used 50 μM 7-benzyloxy-4-(trifluoromethyl)-coumarin as substrate). Detection was based on spectrofluorimetric quantitation of the enzymatic product produced. Assays for the other targets were radioligand binding assays. <b>Assay Cutoff:</b> A response of ≥ 50% inhibition was considered active.</p><p><a class="figpopup" href="/books/NBK143551/table/ml250.t2/?report=objectonly" target="object" rid-figpopup="figml250t2" rid-ob="figobml250t2">Table 2</a> gives an overview of the PubChem assays associated with the GPR7 antagonist project and indicates which are associated with the current probe development effort for <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250t2"><a href="/books/NBK143551/table/ml250.t2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figml250t2" rid-ob="figobml250t2"><img class="small-thumb" src="/books/NBK143551/table/ml250.t2/?report=thumb" src-large="/books/NBK143551/table/ml250.t2/?report=previmg" alt="Table 2. Overview of PubChem assays for GPR7 antagonist project." /></a><div class="icnblk_cntnt"><h4 id="ml250.t2"><a href="/books/NBK143551/table/ml250.t2/?report=objectonly" target="object" rid-ob="figobml250t2">Table 2</a></h4><p class="float-caption no_bottom_margin">Overview of PubChem assays for GPR7 antagonist project. </p></div></div></div></div><div id="ml250.s16"><h3>2.2. Probe Chemical Characterization</h3><div id="ml250.fu2" class="figure bk_fig"><div class="graphic"><img src="/books/NBK143551/bin/ml250fu3.jpg" alt="CID 50904505 SID 110923218 ML250." /></div><h3><span class="title">CID 50904505<br />SID 110923218<br />ML250</span></h3></div><p>The probe structure was verified by NMR and high resolution MS. Purity was assessed to be greater than 95% by LC-MS (<a class="figpopup" href="/books/NBK143551/figure/ml250.f1/?report=objectonly" target="object" rid-figpopup="figml250f1" rid-ob="figobml250f1">Figure 1</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml250f1" co-legend-rid="figlgndml250f1"><a href="/books/NBK143551/figure/ml250.f1/?report=objectonly" target="object" title="Figure 1" class="img_link icnblk_img figpopup" rid-figpopup="figml250f1" rid-ob="figobml250f1"><img class="small-thumb" src="/books/NBK143551/bin/ml250f1.gif" src-large="/books/NBK143551/bin/ml250f1.jpg" alt="Figure 1. LC-MS results for probe ML250." /></a><div class="icnblk_cntnt" id="figlgndml250f1"><h4 id="ml250.f1"><a href="/books/NBK143551/figure/ml250.f1/?report=objectonly" target="object" rid-ob="figobml250f1">Figure 1</a></h4><p class="float-caption no_bottom_margin">LC-MS results for probe ML250. </p></div></div><p>The solubility of probe compound <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> in PBS (137 mM NaCl, 2.7 mM KCl, 10 mM sodium phosphate dibasic, 2 mM potassium phosphate monobasic, pH 7.4) at 23 °C was determined to be 0.17 μM, and the probe has a half-life of > 48 hours in PBS at 23 °C (95% compound remaining at 48 hours) (<a class="figpopup" href="/books/NBK143551/figure/ml250.f2/?report=objectonly" target="object" rid-figpopup="figml250f2" rid-ob="figobml250f2">Figure 2</a>).</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml250f2" co-legend-rid="figlgndml250f2"><a href="/books/NBK143551/figure/ml250.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml250f2" rid-ob="figobml250f2"><img class="small-thumb" src="/books/NBK143551/bin/ml250f2.gif" src-large="/books/NBK143551/bin/ml250f2.jpg" alt="Figure 2. Stability of probe ML250 in PBS." /></a><div class="icnblk_cntnt" id="figlgndml250f2"><h4 id="ml250.f2"><a href="/books/NBK143551/figure/ml250.f2/?report=objectonly" target="object" rid-ob="figobml250f2">Figure 2</a></h4><p class="float-caption no_bottom_margin">Stability of probe ML250 in PBS. </p></div></div><p>No Michael acceptor adducts were observed when a sample of the probe was incubated with 50 μM glutathione for 6 hours and analyzed by LC-MS.</p><p>The following compounds (<a class="figpopup" href="/books/NBK143551/table/ml250.t3/?report=objectonly" target="object" rid-figpopup="figml250t3" rid-ob="figobml250t3">Table 3</a>) have been submitted to the SMR collection. Compound numbers (column 2) refer to <a class="figpopup" href="/books/NBK143551/table/ml250.t4/?report=objectonly" target="object" rid-figpopup="figml250t4" rid-ob="figobml250t4">Table 4</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250t3"><a href="/books/NBK143551/table/ml250.t3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml250t3" rid-ob="figobml250t3"><img class="small-thumb" src="/books/NBK143551/table/ml250.t3/?report=thumb" src-large="/books/NBK143551/table/ml250.t3/?report=previmg" alt="Table 3. Compounds submitted to the MLSMR." /></a><div class="icnblk_cntnt"><h4 id="ml250.t3"><a href="/books/NBK143551/table/ml250.t3/?report=objectonly" target="object" rid-ob="figobml250t3">Table 3</a></h4><p class="float-caption no_bottom_margin">Compounds submitted to the MLSMR. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250t4"><a href="/books/NBK143551/table/ml250.t4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml250t4" rid-ob="figobml250t4"><img class="small-thumb" src="/books/NBK143551/table/ml250.t4/?report=thumb" src-large="/books/NBK143551/table/ml250.t4/?report=previmg" alt="Table 4. SAR Table." /></a><div class="icnblk_cntnt"><h4 id="ml250.t4"><a href="/books/NBK143551/table/ml250.t4/?report=objectonly" target="object" rid-ob="figobml250t4">Table 4</a></h4><p class="float-caption no_bottom_margin">SAR Table. </p></div></div></div><div id="ml250.s17"><h3>2.3. Probe Preparation</h3><div id="ml250.f3" class="figure bk_fig"><div class="graphic"><img src="/books/NBK143551/bin/ml250f3.jpg" alt="Figure 3. Synthesis scheme for ML250 (CYM50769)." /></div><h3><span class="label">Figure 3</span><span class="title">Synthesis scheme for ML250 (CYM50769)</span></h3></div><p>MOMCl was added to a suspension of 4,5-dichloropyridazin-3-one <b>1</b>, DIPEA and DMAP in CH<sub>2</sub>Cl<sub>2</sub> at 0 °C over a period of 30 minutes. The reaction was stirred at room temperature overnight. The organic phase was washed with 2M NaHCO<sub>3</sub> (2X), dried over sodium sulfate and concentrated under reduced pressure. The mixture was purified by column chromatography (CC) (hexanes/EtOAc, 7:3) to give pyridazinone <b>2</b> in 85% yield.</p><p>NaH was slowly added to a solution of 4-methoxyphenol in 1,4-dioxane at 15 °C and the mixture was stirred for 30 minutes. Pyridazinone <b>2</b> was slowly added to the reaction mixture at 15–20 °C over a period of 10 minutes and the reaction was stirred overnight at room temperature. The mixture was quenched with H<sub>2</sub>O and the product extracted with EtOAc. The organic phase was washed with brine (2X), dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by CC (CH<sub>2</sub>Cl<sub>2</sub>/EtOAc, 9:1) to furnish pyridazinone <b>3</b> in 65% yield.</p><p>BBr<sub>3</sub> (1M in CH<sub>2</sub>Cl<sub>2</sub>) was added to a solution of <b>3</b> in CH<sub>2</sub>Cl<sub>2</sub> at -78 °C and the mixture was stirred for 10 minutes at -78 °C followed by 1 hour at room temperature. The mixture was quenched with water and the product extracted with EtOAc. The organic phase was dried over sodium sulfate and concentrated to give pyridazinone <b>4</b> in 93% yield. Compound <b>4</b> was used without further purification.</p><p>A mixture of pyridazinone <b>4</b>, 9-bromofluorene and K<sub>2</sub>CO<sub>3</sub> in DMF was stirred for 24 hours at room temperature. The mixture was diluted with EtOAc and washed with brine (3X). The organic phase was dried over sodium sulfate and concentrated. The crude compound was purified by CC (hexanes/EtOAc, 8:2) to furnish <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> in 66% yield.</p><p><sup>1</sup>H NMR and <sup>13</sup>C NMR results of 5-chloro-2-(9<i>H</i>-fluoren-9-yl)-4-(4-methoxyphenoxy)pyridazin-3(2<i>H</i>)-one (<a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a>) are as follows: <sup>1</sup>H NMR (600 MHz, CDCl<sub>3</sub>): <i>δ</i> 7.75 (d, <i>J</i> = 7.5 Hz, 2H), 7.62 (s, 1H), 7.43 (t, <i>J</i> = 7.5 Hz, 2H), 7.35 (d, <i>J</i> = 7.5 Hz, 1H), 7.28 (t, <i>J</i> = 7.5 Hz, 2H), 7.15 (bs, 1H), 7.04 (d, <i>J</i> = 8.7 Hz, 2H), 6.92 (d, <i>J</i> = 8.7 Hz, 2H), 3.82 (s, 3H); <sup>13</sup>C NMR (150 MHz, CDCl<sub>3</sub>): <i>δ</i> 157.80, 156.33, 149.79, 148.20, 142.59, 141.52, 138.00, 129.27, 127.95, 127.11, 125.05, 120.54, 117.81, 114.88, 63.51, 55.72. MS (EI) <i>m/z</i>: 417 (M<sup>+</sup>).</p></div></div><div id="ml250.s18"><h2 id="_ml250_s18_">3. Results</h2><p><a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> inhibits human GPR7 expression in the presence of a GPR7 agonist NPW with an IC50 of 124nM–244nM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540365" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540365</a>). In a counterscreen for MCH1 antagonism in the presence of an agonist, <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> has an IC50 of >20 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540371" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540371</a>), for a 82 – >161-fold selectivity for GPR7. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is nontoxic to U2OS cells, with a CC50 of > 20 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588326" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 588326</a>).</p><div id="ml250.s19"><h3>3.1. Summary of Screening Results</h3><p>The uHTS screening strategy for this project is shown in <a class="figpopup" href="/books/NBK143551/figure/ml250.f4/?report=objectonly" target="object" rid-figpopup="figml250f4" rid-ob="figobml250f4">Figure 4</a>. In the primary cell-based uHTS assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>), 290K compounds were screened using a fluorogenic intracellular calcium indicator. A total of 3157 compounds (1.1%) were active. 2380 out of these 3157 compounds were available. For the uHTS confirmation assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>), these 2380 active compounds were retested in triplicate, and 1246 compounds (52.4%) were confirmed as active. These 1246 confirmed active compounds were tested in triplicate in a uHTS counterscreen assay against MCH1 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a>), and 130 compounds were found to be inactive against MCH1. 126 out of these 130 compounds were available and were tested in a dose response assay against GPR7 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2251</a>). 19 out of the 126 compounds had an IC50 < 10 μM. These 19 compounds were tested in a dose response counterscreen assay against MCH1, and 18 were found to be inactive, with an IC50 > 10 μM.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml250f4" co-legend-rid="figlgndml250f4"><a href="/books/NBK143551/figure/ml250.f4/?report=objectonly" target="object" title="Figure 4" class="img_link icnblk_img figpopup" rid-figpopup="figml250f4" rid-ob="figobml250f4"><img class="small-thumb" src="/books/NBK143551/bin/ml250f4.gif" src-large="/books/NBK143551/bin/ml250f4.jpg" alt="Figure 4. GPR7 antagonist HTS overview." /></a><div class="icnblk_cntnt" id="figlgndml250f4"><h4 id="ml250.f4"><a href="/books/NBK143551/figure/ml250.f4/?report=objectonly" target="object" rid-ob="figobml250f4">Figure 4</a></h4><p class="float-caption no_bottom_margin">GPR7 antagonist HTS overview. </p></div></div></div><div id="ml250.s20"><h3>3.2. Dose Response Curve for Probe</h3><div id="ml250.f5" class="figure bk_fig"><div class="graphic"><img src="/books/NBK143551/bin/ml250f5.jpg" alt="Figure 5. Dose response curve for ML250." /></div><h3><span class="label">Figure 5</span><span class="title">Dose response curve for ML250</span></h3></div><p>Maximum inhibition is not achieved until ~1 μM <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a>, indicating that in the assay media <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is present in higher concentration than in the solubility assay. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> may be more soluble in assay media than in PBS.</p></div><div id="ml250.s21"><h3>3.3. Scaffold/Moiety Chemical Liabilities</h3><p>No reactive functional groups are observed in the probe molecule, which is very stable with a half-life of > 48 hours.</p></div><div id="ml250.s22"><h3>3.4. SAR Table</h3><p><a class="figpopup" href="/books/NBK143551/table/ml250.t4/?report=objectonly" target="object" rid-figpopup="figml250t4" rid-ob="figobml250t4">Table 4</a> shows structures of compounds used for probe optimization.</p><p>The HTS hit compound CID 1479652 (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/17409616" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 17409616</a>, compound <b>1</b>) does not contain reactive intermediates and its synthetic manipulation is feasible, making this compound suitable for further development. CID 1479652 was resynthesized (<a href="https://pubchem.ncbi.nlm.nih.gov/substance/93375574" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 93375574</a>) with a confirmed IC50 of 2.2 μM and was selected for medicinal chemistry optimization.</p><p><i><u>SAR of R group</u>:</i> The benzyl analog (<b>2</b>) was 2–3-fold more potent than the hit compound. Attaching a methyl (<b>3</b>) or a trifluoromethyl (<b>5</b>) group in ortho, two methyl groups in meta (<b>6</b>), or two fluorine groups in ortho (<b>4</b>) led to more active compounds than compound <b>2</b>. The naphthalen-1-yl methyl analog (<b>8</b>) was 6-fold more potent but slightly less selective than compound <b>2</b>, whereas the naphatalen-2-yl analog (<b>7</b>) was slightly less potent. Substitution at the benzylic position with an ethoxycarbonyl (<b>9</b>) or a phenyl group (<b>10</b>) led to similar or 2-fold increase in potency compared to compound <b>2</b>, respectively. The anthracen-9-yl derivative (<b>11</b>) was equipotent to compound <b>10</b>. The 2-methylnaphthalen-1-yl analog (<b>12</b>) was slightly less potent and selective against MCH1 than compound <b>8</b>. Contrary to the phenyl series, the 2-(naphthalene-1-yl) ethyl acetate (<b>13</b>) was 4-fold less potent than compound <b>8</b>. The installation of a basic nitrogen (<b>14</b>) in the naphthalenyl ring led to a substantial loss of potency. Introducing into the biphenyl system of compound <b>10</b> a carbonyl group between the phenyl rings (<b>15</b>), or an ethanoyl group (<b>16</b>) between the biphenyl and pyridazinone ring, led to slightly decrease and slight increase of potency, respectively. The rotationally restricted biaryl system <b>17</b> was 2-fold more potent and significantly more selective than the parent compound <b>10</b>. The 1,1′-biphenyl-2-yl derivative compound <b>18</b> was slightly more potent than compound <b>10</b>.</p><p><i><u>SAR of Ar group</u>:</i> Increasing the length of the para substituent of the phenyl ring in the Ar portion (<b>19</b>, <b>20</b>) led to a decrease in potency correlated to the length of the substituent. The ethyl analog <b>21</b> was equipotent to the methoxy analog compound <b>8</b>, indicating that the oxygen was not fundamental for the binding. The 2,3-hydrobenzofuran (<b>22</b>) was 2-fold less potent than compound <b>8</b>. The SAR at the Ar portion of the fluorene series (<b>23</b>, <b>24</b>) followed the trend of the naphthalene-1-yl series. Among the modifications of the ether linker located between the Ar portion and the pyridazinone nucleus, thioether (<b>26</b>) was 4-fold less potent whereas the aza analog (<b>25</b>) was 75-fold less potent than compound <b>8</b>.</p><p><i><u>SAR of X group</u>:</i> With respect to modifications of substituent X at position 5 of the pyridazinone, the bromo analog (<b>27</b>) was slightly less potent than the chloro (<b>8)</b> whereas the cyanide (<b>28)</b> and the sulfoxyde (<b>29</b>) were 9- and 11-fold less potent, respectively.</p><p><i><u>SAR of Y group</u>:</i> Interestingly, introducing a cyanide group at position 6 (<b>30</b>) led to 2–3-fold decrease in potency compared to compound <b>3</b> while the 5,6-diethylene derivative (<b>31</b>) was 1–2 fold less potent. Finally, the 6-bromo analog (<b>32</b>) was equipotent and more selective than compound <b>8</b>.</p><p><i><u>SAR Summary</u>:</i> Compounds <b>8</b>, <b>17</b>, <b>21</b>, and <b>23</b> were approximately equipotent, but compound <b>17</b> was the most selective and was thus chosen as the probe.</p></div><div id="ml250.s23"><h3>3.5. Cellular Activity</h3><p>The primary GPR7 inhibition assay is a cell-based assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a>, and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2251</a>), as is the MCH1 cell-based counterscreen assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2257</a>). <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> was tested in a cytotoxicity assay (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588326" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 588326</a>), where no cytotoxicity was observed in U2OS cells at 20 μM, the highest concentration tested. Thus the probe compound has been tested in three cellular assays.</p></div><div id="ml250.s24"><h3>3.6. Profiling Assays</h3><p>To date, the lead hit compound <b>1</b> (CID 1479652) has been tested in 470 other bioassays deposited in PubChem, and has shown activity in only nine of those assays, four of which are for the GPR7 antagonist project. The other five assays give a hit rate of 0.01%, indicating that this series is generally inactive across a broad range of cell-based and non-cell based assays.</p><p>Compound <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> was submitted to Ricerca Biosciences, LLC for HitProfilingScreen + CYP450 (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540332" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540332</a>) for selectivity profiling. The purpose of this panel of binding assays was to identify potential receptors, transporters, or ion channels for which compound <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> displays affinity. Out of 35 targets tested, three (CYP450 1A2, CYP450 2C19, and serotonin [5-hydroxytryptamine] 5-HT<sub>2B</sub>) resulted in modest inhibition of activity when tested at 30 μM (<a class="figpopup" href="/books/NBK143551/table/ml250.t5/?report=objectonly" target="object" rid-figpopup="figml250t5" rid-ob="figobml250t5">Table 6</a>). If these compounds have normal dose response curves the IC50s will clearly be in the double-digit micromolar range. These data suggest that <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is generally inactive against a broad array of off targets and does not likely exert unwanted effects.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml250t5"><a href="/books/NBK143551/table/ml250.t5/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figml250t5" rid-ob="figobml250t5"><img class="small-thumb" src="/books/NBK143551/table/ml250.t5/?report=thumb" src-large="/books/NBK143551/table/ml250.t5/?report=previmg" alt="Table 6. Targets that exhibited ≥50% in Ricerca screening." /></a><div class="icnblk_cntnt"><h4 id="ml250.t5"><a href="/books/NBK143551/table/ml250.t5/?report=objectonly" target="object" rid-ob="figobml250t5">Table 6</a></h4><p class="float-caption no_bottom_margin">Targets that exhibited ≥50% in Ricerca screening. </p></div></div></div></div><div id="ml250.s25"><h2 id="_ml250_s25_">4. Discussion</h2><p>Probe <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> inhibits human GPR7 expression in the presence of a GPR7 agonist with an IC50 of 124 nM–244 nM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540365" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540365</a>). In a counterscreen for MCH1 antagonism in the presence of agonist NPW, it has an IC50 of > 20 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540371" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540371</a>), for a 82 – >161-fold selectivity for GPR7. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is nontoxic to U2OS cells, with a CC50 of > 20 μM (<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588326" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 588326</a>). <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> is suitable for use in cell-based assays, where the compound can be delivered in sufficient concentration. ADMET and PK optimization is required for a compound that would be useful for <i>in vivo</i> studies.</p><div id="ml250.s26"><h3>4.1. Comparison to existing art and how the new probe is an improvement</h3><p>We previously reported probe <a href="/pcsubstance/?term=ML181[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML181</a>, a 272 nM antagonist that is 14-fold selective for GPR7 over the antitarget MCH1, which was the first reported small molecule modulator of GPR7 (<a class="bibr" href="#ml250.r21" rid="ml250.r21">21</a>). To our knowledge, no other potent, selective small molecule inhibitors or antagonists of GPR7 have been reported. <a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> has comparable potency (124 nM–244 nM) but greater selectivity (82 – >161 fold) than <a href="/pcsubstance/?term=ML181[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML181</a>.</p></div><div id="ml250.s27"><h3>4.2. Mechanism of Action Studies</h3><p>An intracellular calcium release assay was performed. Although GPR7 is naturally coupled to Gαi (<a class="bibr" href="#ml250.r17" rid="ml250.r17">17</a>), which decreases cAMP levels upon activation, this assay employs a chimeric cell line that forces the receptor to use Gqi3, and therefore the assay readout is calcium release. The probe compound was effective at inhibiting calcium release in this assay, indicating that the probe interacts with GPR7 to inhibit downstream signaling events.</p></div><div id="ml250.s28"><h3>4.3. Planned Future Studies</h3><p><a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a> represents a promising start point to initiate a lead-optimization program in order to develop innovative GPR7 antagonists with an improved potency and selectivity profile, and desirable pharmacokinetic and toxicokinetic properties suitable for clinical development. In addition to simple analogue SAR, we hope to perform in-house scaffold hopping using available software to identify a second or third generation chemotype. The most promising compounds will be tested for selectivity against a panel of off-target proteins including GPCRs and ion channels. Dr. Civelli will perform experiments using animal models of neuropathic and inflammatory pain, including analgesic effects observed in the paw flick test and formalin test in rats, the behavioral response observed after acute thermal stimuli or chemically induced pain (<a class="bibr" href="#ml250.r1" rid="ml250.r1">1</a>, <a class="bibr" href="#ml250.r9" rid="ml250.r9">9</a>), and a ligation-induced nerve injury model (<a class="bibr" href="#ml250.r10" rid="ml250.r10">10</a>, <a class="bibr" href="#ml250.r20" rid="ml250.r20">20</a>).</p></div></div><div id="ml250.s29"><h2 id="_ml250_s29_">5. References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ml250.r1">Bosier B, Hermans E. Versatility of GPCR recognition by drugs: from biological implications to therapeutic relevance. <span><span class="ref-journal">Trends Pharmacol Sci. </span>2007;<span class="ref-vol">28</span>:438–446.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17629964" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17629964</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ml250.r2">Lagerstrom MC, Schioth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. <span><span class="ref-journal">Nat Rev Drug Discov. </span>2008;<span class="ref-vol">7</span>:339–357.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18382464" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18382464</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ml250.r3">Pan HL, Wu ZZ, Zhou HY, Chen SR, Zhang HM, Li DP. Modulation of pain transmission by G-protein-coupled receptors. <span><span class="ref-journal">Pharmacol Ther. </span>2008;<span class="ref-vol">117</span>:141–161.</span> [<a href="/pmc/articles/PMC2965406/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2965406</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17959251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17959251</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ml250.r4">Thompson MD, Cole DE, Jose PA. Pharmacogenomics of G protein-coupled receptor signaling: insights from health and disease. <span><span class="ref-journal">Methods Mol Biol. </span>2008;<span class="ref-vol">448</span>:77–107.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18370232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18370232</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ml250.r5">Tanaka H, Yoshida T, Miyamoto N, Motoike T, Kurosu H, Shibata K, Yamanaka A, Williams SC, Richardson JA, Tsujino N, Garry MG, Lerner MR, King DS, O’Dowd BF, Sakurai T, Yanagisawa M. Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2003;<span class="ref-vol">100</span>:6251–6256.</span> [<a href="/pmc/articles/PMC156358/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC156358</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12719537" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12719537</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ml250.r6">Brezillon S, Lannoy V, Franssen JD, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M. Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8. <span><span class="ref-journal">J Biol Chem. </span>2003;<span class="ref-vol">278</span>:776–783.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12401809" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12401809</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ml250.r7">Fujii R, Yoshida H, Fukusumi S, Habata Y, Hosoya M, Kawamata Y, Yano T, Hinuma S, Kitada C, Asami T, Mori M, Fujisawa Y, Fujino M. Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7. <span><span class="ref-journal">J Biol Chem. </span>2002;<span class="ref-vol">277</span>:34010–34016.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12118011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12118011</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="ml250.r8">Ishii M, Fei H, Friedman JM. Targeted disruption of GPR7, the endogenous receptor for neuropeptides B and W, leads to metabolic defects and adult-onset obesity. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2003;<span class="ref-vol">100</span>:10540–10545.</span> [<a href="/pmc/articles/PMC193597/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC193597</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12925742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12925742</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="ml250.r9">Kelly MA, Beuckmann CT, Williams SC, Sinton CM, Motoike T, Richardson JA, Hammer RE, Garry MG, Yanagisawa M. Neuropeptide B-deficient mice demonstrate hyperalgesia in response to inflammatory pain. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2005;<span class="ref-vol">102</span>:9942–9947.</span> [<a href="/pmc/articles/PMC1174999/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1174999</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15983370" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15983370</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="ml250.r10">Zaratin PF, Quattrini A, Previtali SC, Comi G, Hervieu G, Scheideler MA. Schwann cell overexpression of the GPR7 receptor in inflammatory and painful neuropathies. <span><span class="ref-journal">Mol Cell Neurosci. </span>2005;<span class="ref-vol">28</span>:55–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15607941" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15607941</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="ml250.r11">Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. <span><span class="ref-journal">Trends Neurosci. </span>2002;<span class="ref-vol">25</span>:319–325.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12086751" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12086751</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="ml250.r12">Lee DK, Nguyen T, Porter CA, Cheng R, George SR, O’Dowd BF. Two related G protein-coupled receptors: the distribution of GPR7 in rat brain and the absence of GPR8 in rodents. <span><span class="ref-journal">Brain Res Mol Brain Res. </span>1999;<span class="ref-vol">71</span>:96–103.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10407191" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10407191</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="ml250.r13">Ahmad S, Dray A. Novel G protein-coupled receptors as pain targets. <span><span class="ref-journal">Curr Opin Investig Drugs. </span>2004;<span class="ref-vol">5</span>:67–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14983976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14983976</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="ml250.r14">Annemans L. Pharmacoeconomic impact of adverse events of long-term opioid treatment for the management of persistent pain. <span><span class="ref-journal">Clin Drug Investig. </span>2011;<span class="ref-vol">31</span>:73–86.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21067250" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21067250</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="ml250.r15">Fine PG. Long-term consequences of chronic pain: mounting evidence for pain as a neurological disease and parallels with other chronic disease States. <span><span class="ref-journal">Pain Med. </span>2011;<span class="ref-vol">12</span>:996–1004.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21752179" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21752179</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="ml250.r16">Sinatra R. Causes and consequences of inadequate management of acute pain. <span><span class="ref-journal">Pain Med. </span>2010;<span class="ref-vol">11</span>:1859–1871.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21040438" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21040438</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="ml250.r17">Singh G, Davenport AP. Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system. <span><span class="ref-journal">Br J Pharmacol. </span>2006;<span class="ref-vol">148</span>:1033–1041.</span> [<a href="/pmc/articles/PMC1752024/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1752024</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16847439" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16847439</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="ml250.r18">O’Dowd BF, Scheideler MA, Nguyen T, Cheng R, Rasmussen JS, Marchese A, Zastawny R, Heng HH, Tsui LC, Shi X, et al. The cloning and chromosomal mapping of two novel human opioid-somatostatin-like receptor genes, GPR7 and GPR8, expressed in discrete areas of the brain. <span><span class="ref-journal">Genomics. </span>1995;<span class="ref-vol">28</span>:84–91.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/7590751" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7590751</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="ml250.r19">Shimomura Y, Harada M, Goto M, Sugo T, Matsumoto Y, Abe M, Watanabe T, Asami T, Kitada C, Mori M, Onda H, Fujino M. Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8. <span><span class="ref-journal">J Biol Chem. </span>2002;<span class="ref-vol">277</span>:35826–35832.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12130646" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12130646</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="ml250.r20">Yamamoto T, Saito O, Shono K, Tanabe S. Effects of intrathecal and i.c.v. administration of neuropeptide W-23 and neuropeptide B on the mechanical allodynia induced by partial sciatic nerve ligation in rats. <span><span class="ref-journal">Neuroscience. </span>2006;<span class="ref-vol">137</span>:265–273.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16289588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16289588</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="ml250.r21">Guerrero M, Urbano M, Wang Z, Zhao J, Velaparthi S, Schaeffer M-T, Brown SJ, Saldanha SA, Chase P, Ferguson J, Civelli O, Roberts E, Hodder P, Rosen H. Optimization and Characterization of an Antagonist for G-protein Coupled Receptor 7 (GPR7). <span><span class="ref-journal">MLPCN probe report. </span>2010</span></div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="ml250.r22">Li X, He Y, Ruiz CH, Koenig M, Cameron MD, Vojkovsky T. Characterization of dasatinib and its structural analogs as CYP3A4 mechanism-based inactivators and the proposed bioactivation pathways. <span><span class="ref-journal">Drug Metab Dispos. </span>2009;<span class="ref-vol">37</span>:1242–1250.</span> [<a href="/pmc/articles/PMC3202349/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3202349</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19282395" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19282395</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="ml250.r23">Li X, Kamenecka TM, Cameron MD. Bioactivation of the epidermal growth factor receptor inhibitor gefitinib: implications for pulmonary and hepatic toxicities. <span><span class="ref-journal">Chem Res Toxicol. </span>2009;<span class="ref-vol">22</span>:1736–1742.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19803472" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19803472</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK143551_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Miguel Guerrero</span>,<sup>*</sup> <span itemprop="author">Mariangela Urbano</span>,<sup>*</sup> <span itemprop="author">Zhiwei Wang</span>,<sup>†</sup> <span itemprop="author">Jian Zhao</span>,<sup>*</sup> <span itemprop="author">Subash Velaparthi</span>,<sup>*</sup> <span itemprop="author">Marie-Therese Schaeffer</span>,<sup>‡</sup> <span itemprop="author">Steven J Brown</span>,<sup>‡</sup> <span itemprop="author">S Adrian Saldanha</span>,<sup>§</sup> <span itemprop="author">Peter Chase</span>,<sup>§</sup> <span itemprop="author">Jill Ferguson</span>,<sup>‡</sup> <span itemprop="author">Peter Hodder</span>,<sup>§</sup> <span itemprop="author">Hugh Rosen</span>,<sup>‡</sup><sup>,1</sup> <span itemprop="author">Olivier Civelli</span>,<sup>†</sup> and <span itemprop="author">Edward Roberts</span><sup>*</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>*</sup>
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Department of Chemistry, The Scripps Research Institute Molecular Screening Center, The Scripps Research Institute, La Jolla, CA 92037</div><div class="affiliation"><sup>†</sup>
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Department of Pharmacology, University of California, Irvine, Irvine, CA 92697</div><div class="affiliation"><sup>‡</sup>
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Department of Chemical Physiology, The Scripps Research Institute Molecular Screening Center, The Scripps Research Institute, La Jolla, CA 92037</div><div class="affiliation"><sup>§</sup>
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Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458</div><div class="affiliation"><sup>1</sup> Corresponding author:
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<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.sppircs@nesorh" class="oemail">ude.sppircs@nesorh</a></div><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p>National Center for Biotechnology Information (US), Bethesda (MD)</p><h3>NLM Citation</h3><p>Guerrero M, Urbano M, Wang Z, et al. Optimization and Characterization of a Second Antagonist for G-protein Coupled Receptor 7 (GPR7) In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/mlprobe/ml251/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/mlprobe/ml249/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="fig" id="figobml250fu1"><div id="ml250.fu1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK143551/bin/ml250fu1.jpg" alt="ML250." /></div><h3><span class="title">ML250</span></h3></div></article><article data-type="table-wrap" id="figobml250tu1"><div id="ml250.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml250.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID/ML#</th><th id="hd_h_ml250.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target Name</th><th id="hd_h_ml250.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC50 (nM) [SID, AID]</th><th id="hd_h_ml250.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti-target Name(s)</th><th id="hd_h_ml250.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC50 (μM) [SID, AID]</th><th id="hd_h_ml250.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Fold Selective</th><th id="hd_h_ml250.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary Assay(s) Name: IC50 (nM) [SID, AID]</th></tr></thead><tbody><tr><td headers="hd_h_ml250.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 50904505/<a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a></td><td headers="hd_h_ml250.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">GPR7</td><td headers="hd_h_ml250.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">124nM–244nM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540365" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540365</a>]</td><td headers="hd_h_ml250.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MCH1</td><td headers="hd_h_ml250.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>20Mm<br /><br /><br />[<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540371" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540371</a>]</td><td headers="hd_h_ml250.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">82 – >161</td><td headers="hd_h_ml250.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>GPR7 ANT:</b> 124–244 nM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540365" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540365</a>]<br /><b>MCH1 ANT:</b> >20μM [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540371" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540371</a>]<br /><b>Cytotoxicity:</b> CC50 > 20μM: [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588326" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 588326</a>]<br /><b>Ricerca screening:</b> [<a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540345" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540345</a>]</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml250t1"><div id="ml250.t1" class="table"><h3><span class="label">Table 1</span><span class="title">Published GPR7 antagonist</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.t1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.t1_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml250.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Structure</th><th id="hd_h_ml250.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">IC50 for GPR7</th><th id="hd_h_ml250.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Selectivity</th><th id="hd_h_ml250.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reference</th></tr></thead><tbody><tr><td headers="hd_h_ml250.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu2.jpg" alt="Image ml250fu2.jpg" /></div></td><td headers="hd_h_ml250.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">272 nM</td><td headers="hd_h_ml250.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14-fold over MCH1</td><td headers="hd_h_ml250.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">(<a class="bibr" href="#ml250.r21" rid="ml250.r21">21</a>)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml250t2"><div id="ml250.t2" class="table"><h3><span class="label">Table 2</span><span class="title">Overview of PubChem assays for GPR7 antagonist project</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AID</th><th id="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Name</th><th id="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Tested/Active</th><th id="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Non-ML Tested</th><th id="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Purch Tested/Active</th><th id="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Synth Tested/Active</th></tr></thead><tbody><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1861" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1861</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fluorescence-based primary cell-based high throughput screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">290735/3127</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 1952</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fluorescence-based confirmation cell-based high throughput screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2380/1246</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2148" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2148</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fluorescence-based counterscreen for antagonists of the G-protein coupled receptor 7 (GPR7): cell-based high throughput screening assay to identify antagonists of the melanin-concentrating hormone receptor 1 (MCHR1)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2380/1470</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2251</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fluorescence-based dose response cell-based high throughput screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">126/19</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 2257</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fluorescence-based counterscreen for antagonists of the G-protein coupled receptor 7 (GPR7): cell-based high throughput dose response assay to identify antagonists of the melanin-concentrating hormone receptor 1 (MCHR1).</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">126/7</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463251" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463251</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based dose response cell-based screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">88/66</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">88</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">88/66</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463250" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463250</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based counterscreen for antagonists of the G-protein coupled receptor 7 (GPR7): cell-based dose response assay to identify antagonists of the melanin-concentrating hormone receptor 1 (MCHR1)</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">85/54</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">85</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">85/54</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/463253" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 463253</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage luminescence-based cell-based dose response assay to identify antagonists of the G-protein coupled receptor 7 (GPR7): Cytotoxicity assay</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/485339" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 485339</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based dose response cell-based screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7): Intracellular calcium release</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/1</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/1</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504401" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 504401</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage counterscreen panel assay for GPR7 antagonists: Ricerca HitProfilingScreen + CYP450</td><td headers="hd_h_ml250.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td></tr><tr><th headers="hd_h_ml250.t2_1_1_1_1 hd_h_ml250.t2_1_1_1_2 hd_h_ml250.t2_1_1_1_3 hd_h_ml250.t2_1_1_1_4 hd_h_ml250.t2_1_1_1_5 hd_h_ml250.t2_1_1_1_6" id="hd_b_ml250.t2_1_1_11_1" colspan="6" rowspan="1" style="text-align:center;vertical-align:middle;">The AIDs below are for the new current probe development effort (<a href="/pcsubstance/?term=ML250[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML250</a>)</th></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504868" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 504868</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based dose response cell-based screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7) Set 2</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">25/22</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">25</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/1</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">24/21</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504886" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 504886</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage results from the probe development effort to identify antagonists of the G-protein coupled receptor 7 (GPR7): luminescence-based cell-based dose response counterscreen assay to determine cytotoxicity of antagonist compounds Set 2</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/504889" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 504889</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based counterscreen for antagonists of the G-protein coupled receptor 7 (GPR7): cell-based dose response assay to identify antagonists of the melanin-concentrating hormone receptor 1 (MCHR1) Set 2</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">25/15</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">25</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">24/15</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540345" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540345</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage counterscreen panel assay for GPR7 antagonists: Ricerca HitProfilingScreen + CYP450: Set 2</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540365" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540365</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based dose response cell-based screening assay to identify antagonists of the G-protein coupled receptor 7 (GPR7) Set 3</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31/28</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31/18</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/540371" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 540371</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage fluorescence-based counterscreen for antagonists of the G-protein coupled receptor 7 (GPR7): cell-based dose response assay to identify antagonists of the melanin-concentrating hormone receptor 1 (MCHR1) Set 2</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31/15</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">31/15</td></tr><tr><td headers="hd_h_ml250.t2_1_1_1_1 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/588326" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID 588326</a></b></td><td headers="hd_h_ml250.t2_1_1_1_2 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late-stage results from the probe development effort to identify antagonists of the G-protein coupled receptor 7 (GPR7): luminescence-based cell-based dose response counterscreen assay to determine cytotoxicity of antagonist compounds Set 3</td><td headers="hd_h_ml250.t2_1_1_1_3 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td><td headers="hd_h_ml250.t2_1_1_1_4 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml250.t2_1_1_1_5 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0</td><td headers="hd_h_ml250.t2_1_1_1_6 hd_b_ml250.t2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1/0</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml250fu2"><div id="ml250.fu2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK143551/bin/ml250fu3.jpg" alt="CID 50904505 SID 110923218 ML250." /></div><h3><span class="title">CID 50904505<br />SID 110923218<br />ML250</span></h3></div></article><article data-type="fig" id="figobml250f1"><div id="ml250.f1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20LC-MS%20results%20for%20probe%20ML250.&p=BOOKS&id=143551_ml250f1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK143551/bin/ml250f1.jpg" alt="Figure 1. LC-MS results for probe ML250." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">LC-MS results for probe ML250</span></h3></div></article><article data-type="fig" id="figobml250f2"><div id="ml250.f2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Stability%20of%20probe%20ML250%20in%20PBS.&p=BOOKS&id=143551_ml250f2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK143551/bin/ml250f2.jpg" alt="Figure 2. Stability of probe ML250 in PBS." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Stability of probe ML250 in PBS</span></h3></div></article><article data-type="table-wrap" id="figobml250t3"><div id="ml250.t3" class="table"><h3><span class="label">Table 3</span><span class="title">Compounds submitted to the MLSMR</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.t3_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Designation</th><th id="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound Number</th><th id="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th id="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th id="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SRID</th><th id="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th></tr></thead><tbody><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Probe</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>17</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 50904505</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923218</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001098-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675924</td></tr><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Analog 1</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>16</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 53230248</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338657" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 124338657</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001227-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675919</td></tr><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Analog 2</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>32</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 53230249</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338661" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 124338661</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001231-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675920</td></tr><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Analog 3</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>19</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 50904434</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923224" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923224</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001104-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675921</td></tr><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Analog 4</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>27</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 50904496</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923220" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 110923220</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001100-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675922</td></tr><tr><td headers="hd_h_ml250.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>Analog 5</b></td><td headers="hd_h_ml250.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>20</b></td><td headers="hd_h_ml250.t3_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID 51000467</td><td headers="hd_h_ml250.t3_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117682928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 117682928</a></td><td headers="hd_h_ml250.t3_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001098-1</td><td headers="hd_h_ml250.t3_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS003675924</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml250t4"><div id="ml250.t4" class="table"><h3><span class="label">Table 4</span><span class="title">SAR Table</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.t4_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml250.t4_1_1_1_1" colspan="6" rowspan="1" style="text-align:center;vertical-align:middle;">SAR Analysis for GPR7</th><th id="hd_h_ml250.t4_1_1_1_2" colspan="4" rowspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu4.jpg" alt="Image ml250fu4.jpg" /></div></th><th id="hd_h_ml250.t4_1_1_1_3" colspan="4" rowspan="1" style="text-align:center;vertical-align:middle;">Potency (uM) mean ± S.E.M.</th><th id="hd_h_ml250.t4_1_1_1_4" rowspan="3" colspan="1" headers="hd_h_ml250.t4_1_1_1_4" style="text-align:center;vertical-align:middle;">Target to Antitarget Fold Selectivity</th></tr><tr><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" id="hd_h_ml250.t4_1_1_2_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Entry</th><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" id="hd_h_ml250.t4_1_1_2_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">CID</th><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" id="hd_h_ml250.t4_1_1_2_3" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">SID</th><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" id="hd_h_ml250.t4_1_1_2_4" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Center Internal Number SR</th><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" id="hd_h_ml250.t4_1_1_2_5" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Center Internal Number CYM</th><th headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" id="hd_h_ml250.t4_1_1_2_6" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">P/S<sup>†</sup></th><th headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" id="hd_h_ml250.t4_1_1_2_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">R</th><th headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" id="hd_h_ml250.t4_1_1_2_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Ar</th><th headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" id="hd_h_ml250.t4_1_1_2_9" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">X</th><th headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" id="hd_h_ml250.t4_1_1_2_10" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Y</th><th headers="hd_h_ml250.t4_1_1_1_3" id="hd_h_ml250.t4_1_1_2_11" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Target GPR7</th><th headers="hd_h_ml250.t4_1_1_1_3" id="hd_h_ml250.t4_1_1_2_12" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Antitarget MCH1</th></tr><tr><th headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11" id="hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">n<sup>*</sup></th><th headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11" id="hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">IC50<sup>**</sup></th><th headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12" id="hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">n<sup>*</sup></th><th headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12" id="hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">IC50<sup>**</sup></th></tr></thead><tbody><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;"><b>1 (HTS hit)</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">1479652</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17409616" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17409616</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NA</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu5.jpg" alt="Image ml250fu5.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="2" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="2" colspan="1" style="text-align:center;vertical-align:bottom;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.94 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">23.6 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/93375574" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">93375574</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-01000679408-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50434</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.2 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ND</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ND</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>2</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53234167</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124342968" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124342968</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001246-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50845</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu7.jpg" alt="Image ml250fu7.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">784 nM, 1.31 uM, 1.54 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.51 uM, 15.8 uM, 18.5 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.5 – 24</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>3</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904488</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923171" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923171</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001051-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50672</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu8.jpg" alt="Image ml250fu8.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">367 nM, 431 nM, 540 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.06 uM, 7.68 uM, 5.64 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.7–21</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>4</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904483</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923188" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923188</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001068-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50732</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu9.jpg" alt="Image ml250fu9.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">843 nM, 726 nM, 719 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15.6 uM, 15.6 uM, 10.4 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12 – 22</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>5</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904440</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923191" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923191</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001071-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50735</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu10.jpg" alt="Image ml250fu10.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">370 nM, 413 nM, 244 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.49 uM, 4.57 uM, 3.34 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.1 – 19</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>6</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904462</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923143" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923143</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001024-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50708</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu11.jpg" alt="Image ml250fu11.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">411 nM, 626 nM, 646 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.50 uM, 12.1 uM, 6.46 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.3–29</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>7</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904420</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923172" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923172</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001052-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50673</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu12.jpg" alt="Image ml250fu12.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.48 uM, 1.95 uM, 2.02 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.01 uM, 17.0 uM, 10.6 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.0–11</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>8</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904454</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923160" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923160</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001040-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50719</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">143 nM, 232 nM, 220 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">988 nM, 1.70 uM, 1.61 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.3 – 12</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>9</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904507</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923163" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923163</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001043-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50723</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu14.jpg" alt="Image ml250fu14.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.32 uM, 864 nM, 953 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.48 uM, 10.5 uM, 8.11 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.1 – 12</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>10</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904423</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923185" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923185</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001065-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50741</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu15.jpg" alt="Image ml250fu15.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">580 nM, 497 nM, 481 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17.1 uM, > 20 uM, 7.22 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12 – >42</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>11</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904464</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923199" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923199</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001079-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50744</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu16.jpg" alt="Image ml250fu16.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">318 nM, 722 nM, 576 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, 16.7 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">23 – > 63</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>12</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904520</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923204" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923204</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001084-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50755</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu17.jpg" alt="Image ml250fu17.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">222 nM, 232 nM, 202 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">770 nM, 815 nM, 836 nM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.3 – 4.1</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>13</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904514</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923210" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923210</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001090-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50761</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu18.jpg" alt="Image ml250fu18.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">451 nM, 597 nM, 1.31 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15 – 34</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>14</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904494</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923211" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923211</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001091-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50762</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu19.jpg" alt="Image ml250fu19.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.40 uM, 4.10 uM, 4.93 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.15 uM, 4.96 uM, 5.67 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.0 – 1.7</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>15</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904506</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923217" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923217</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001097-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50768</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu20.jpg" alt="Image ml250fu20.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">577 nM, 945 nM, 856 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">12.7 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13 – >35</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>16</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53230248</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338657" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124338657</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001227-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50861</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu21.jpg" alt="Image ml250fu21.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">430 nM, 457 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.92 uM, 2.87 uM, 5.49 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.3 – 13</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>17 (probe)</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904505</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923218" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923218</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001098-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50769</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu22.jpg" alt="Image ml250fu22.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">124 nM, 219 nM, 244 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>82 – >161</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>18</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53230277</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338650" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124338650</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001220-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50854</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu23.jpg" alt="Image ml250fu23.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, 339 nM, 310 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.12 uM, 2.24 uM, 4.59 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><0.056 – 15</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>19</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904434</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923224" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923224</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001104-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50775</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu24.jpg" alt="Image ml250fu24.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">98.0 nM, 571 nM, 744 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.59 uM, 5.22 uM, 6.71 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.1 – 68</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>20</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">51000467</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117682928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">117682928</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001152-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50791</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu25.jpg" alt="Image ml250fu25.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.14 uM, 1.08 uM, 1.12 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">16.0 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14 – 19</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>21</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">51000469</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117682929" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">117682929</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001153-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50792</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu26.jpg" alt="Image ml250fu26.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">245 nM, 218 nM, 232 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.95 uM, 1.72 uM, 2.08 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7.0 – 9.5</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>22</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53230278</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338646" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124338646</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001216-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50852</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu27.jpg" alt="Image ml250fu27.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.22 uM, 480 nM, 456 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7.40 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.3 – 44</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>23</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">51000459</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117682931" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">117682931</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001155-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50793</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu22.jpg" alt="Image ml250fu22.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu24.jpg" alt="Image ml250fu24.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">248 nM, 168 nM, 207 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">81 – 119</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>24</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">51003732</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117687989" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">117687989</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001174-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50826</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu22.jpg" alt="Image ml250fu22.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu25.jpg" alt="Image ml250fu25.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">> 20 uM, > 20 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>25</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904473</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923215" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923215</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001095-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50766</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu28.jpg" alt="Image ml250fu28.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15.5 uM, 9.47 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14.8 uM, 18.1 uM, > 20 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.74 – >2.1</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>26</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53234163</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124342982" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124342982</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001260-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50903</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu29.jpg" alt="Image ml250fu29.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">660 nM, 1.03 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10.6 uM, 12.9 uM, 17.0 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 – 26</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>27</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904496</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923220" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923220</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001100-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50771</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Br</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">132 nM, 242 nM, 240 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">892 nM, 2.14 uM, 1.66 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.7 – 16</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>28</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">51003739</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/117687994" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">117687994</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001179-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50831</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CN</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.31 uM, 1.69 uM, 2.49 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.09 uM, 2.25 uM, 2.22 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.84 – 1.7</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>29</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53230255</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338653" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124338653</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001223-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50857</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu24.jpg" alt="Image ml250fu24.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu30.jpg" alt="Image ml250fu30.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.22 uM, 2.13 uM, 2.09 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6.19 uM, 13.9 uM, 10.8 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.9 – 6.7</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>30</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904429</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923161" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923161</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001041-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50721</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu8.jpg" alt="Image ml250fu8.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CN</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.09 uM, 1.27 uM, 1.19 uM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.52 uM, 2.33 uM, 2.71 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.8 – 2.5</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>31</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50904446</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/110923132" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">110923132</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001013-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50697</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu8.jpg" alt="Image ml250fu8.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu6.jpg" alt="Image ml250fu6.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu31.jpg" alt="Image ml250fu31.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu31.jpg" alt="Image ml250fu31.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">418 nM, 808 nM, 818 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.43 uM, 1.31 uM, 1.45 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.6–3.5</td></tr><tr><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><b>32</b></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">53230249</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/124338661" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">124338661</a></td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SR-02000001231-1</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">50865</td><td headers="hd_h_ml250.t4_1_1_1_1 hd_h_ml250.t4_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu13.jpg" alt="Image ml250fu13.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK143551/bin/ml250fu24.jpg" alt="Image ml250fu24.jpg" /></div></td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml250.t4_1_1_1_2 hd_h_ml250.t4_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Br</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">6</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_11 hd_h_ml250.t4_1_1_3_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">177 nM, 237 nM</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">9</td><td headers="hd_h_ml250.t4_1_1_1_3 hd_h_ml250.t4_1_1_2_12 hd_h_ml250.t4_1_1_3_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.39 uM, 6.02 uM, 16.2 uM</td><td headers="hd_h_ml250.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10 – 92</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>†</dt><dd><div id="ml250.tfn1"><p class="no_margin">P = Purchased; S = Synthesized</p></div></dd></dl><dl class="bkr_refwrap"><dt>*</dt><dd><div id="ml250.tfn2"><p class="no_margin">n = Number of Replicates</p></div></dd></dl><dl class="bkr_refwrap"><dt>**</dt><dd><div id="ml250.tfn3"><p class="no_margin">Each EC50 value is from an independent experiment done in triplicate.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div id="ml250.tfn4"><p class="no_margin">ND = Not determined</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobml250f3"><div id="ml250.f3" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK143551/bin/ml250f3.jpg" alt="Figure 3. Synthesis scheme for ML250 (CYM50769)." /></div><h3><span class="label">Figure 3</span><span class="title">Synthesis scheme for ML250 (CYM50769)</span></h3></div></article><article data-type="fig" id="figobml250f4"><div id="ml250.f4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20GPR7%20antagonist%20HTS%20overview.&p=BOOKS&id=143551_ml250f4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK143551/bin/ml250f4.jpg" alt="Figure 4. GPR7 antagonist HTS overview." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">GPR7 antagonist HTS overview</span></h3></div></article><article data-type="fig" id="figobml250f5"><div id="ml250.f5" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK143551/bin/ml250f5.jpg" alt="Figure 5. Dose response curve for ML250." /></div><h3><span class="label">Figure 5</span><span class="title">Dose response curve for ML250</span></h3></div></article><article data-type="table-wrap" id="figobml250t5"><div id="ml250.t5" class="table"><h3><span class="label">Table 6</span><span class="title">Targets that exhibited ≥50% in Ricerca screening</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK143551/table/ml250.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml250.t5_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml250.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Target</th><th id="hd_h_ml250.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">% Inhibition (30 μM)</th></tr></thead><tbody><tr><td headers="hd_h_ml250.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CYP450, 1A2</td><td headers="hd_h_ml250.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">67</td></tr><tr><td headers="hd_h_ml250.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CYP450, 2C19</td><td headers="hd_h_ml250.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">51</td></tr><tr><td headers="hd_h_ml250.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Serotonin (5-Hydroxytryptamine) 5-HT<sub>2B</sub></td><td headers="hd_h_ml250.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">63</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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