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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Probe Report for NPY-Y2 Receptor Antagonists - 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="Probe Report for NPY-Y2 Receptor Antagonists">
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<meta name="citation_publisher" content="National Center for Biotechnology Information (US)">
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<meta name="citation_date" content="2010/08/06">
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<meta name="citation_author" content="SA Saldanha">
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<meta name="citation_author" content="SP Brothers">
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<meta name="citation_author" content="T Spicer">
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<meta name="citation_author" content="M Cameron">
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<meta name="citation_author" content="BA Mercer">
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<meta name="citation_author" content="P Chase">
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<meta name="citation_author" content="P McDonald">
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<meta name="citation_author" content="C Wahlestedt">
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<meta name="citation_author" content="PS Hodder">
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<meta name="citation_pmid" content="21433370">
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<meta name="DC.Title" content="Probe Report for NPY-Y2 Receptor Antagonists">
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<meta name="DC.Publisher" content="National Center for Biotechnology Information (US)">
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<meta name="DC.Contributor" content="SA Saldanha">
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<meta name="DC.Contributor" content="SP Brothers">
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<meta name="DC.Contributor" content="T Spicer">
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<meta name="DC.Contributor" content="M Cameron">
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<meta name="DC.Contributor" content="BA Mercer">
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<meta name="DC.Contributor" content="P Chase">
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<meta name="DC.Contributor" content="P McDonald">
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<meta name="DC.Contributor" content="C Wahlestedt">
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<meta name="DC.Contributor" content="PS Hodder">
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<meta name="DC.Date" content="2010/08/06">
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<meta name="description" content="Due to its expression profile and biological action, neuropeptide Y (NPY)-Y2 receptor (Y2R) is an attractive G protein-coupled receptor (GPCR) target for anxiolytic research. Additionally, NPY-Y2R is predicted to be a therapeutic target in alcoholism. Four different compounds, ML075 (CID-2936384), ML074 (CID-2228302), ML073 (CID-3236979) and ML072 (CID-4460128) are claimed as novel antagonist probes to the NPY-Y2R, producing increased cAMP (3',5'-cyclic-AMP phosphodiesterase) levels. These probes demonstrate submicromolar affinity to the Y2 receptor, do not antagonize NPY-Y1R, do not present significant cytotoxicity, and are blood-brain barrier penetrant. Hence, these probes represent an improvement over previously described NPY-Y2R antagonists and offer greater promise to serve as valuable in vivo pharmacological probes for elucidating the Y2R signaling pathway.">
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<meta name="og:description" content="Due to its expression profile and biological action, neuropeptide Y (NPY)-Y2 receptor (Y2R) is an attractive G protein-coupled receptor (GPCR) target for anxiolytic research. Additionally, NPY-Y2R is predicted to be a therapeutic target in alcoholism. Four different compounds, ML075 (CID-2936384), ML074 (CID-2228302), ML073 (CID-3236979) and ML072 (CID-4460128) are claimed as novel antagonist probes to the NPY-Y2R, producing increased cAMP (3',5'-cyclic-AMP phosphodiesterase) levels. These probes demonstrate submicromolar affinity to the Y2 receptor, do not antagonize NPY-Y1R, do not present significant cytotoxicity, and are blood-brain barrier penetrant. Hence, these probes represent an improvement over previously described NPY-Y2R antagonists and offer greater promise to serve as valuable in vivo pharmacological probes for elucidating the Y2R signaling pathway.">
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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="_NBK47354_"><span class="title" itemprop="name">Probe Report for NPY-Y2 Receptor Antagonists</span></h1><p class="contribs">Saldanha SA, Brothers SP, Spicer T, et al.</p><p class="fm-aai"><a href="#_NBK47354_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>Due to its expression profile and biological action, neuropeptide Y (NPY)-Y2 receptor (Y2R) is an attractive G protein-coupled receptor (GPCR) target for anxiolytic research. Additionally, NPY-Y2R is predicted to be a therapeutic target in alcoholism. Four different compounds, ML075 (CID-2936384), ML074 (CID-2228302), ML073 (CID-3236979) and ML072 (CID-4460128) are claimed as novel antagonist probes to the NPY-Y2R, producing increased cAMP (3',5'-cyclic-AMP phosphodiesterase) levels. These probes demonstrate submicromolar affinity to the Y2 receptor, do not antagonize NPY-Y1R, do not present significant cytotoxicity, and are blood-brain barrier penetrant. Hence, these probes represent an improvement over previously described NPY-Y2R antagonists and offer greater promise to serve as valuable in vivo pharmacological probes for elucidating the Y2R signaling pathway.</p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> 1 R21 NS056950-01</p><p><b>Screening Center Name & PI:</b> Scripps Research Institute Molecular
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Screening Center (SRIMSC); Hugh Rosen</p><p><b>Chemistry Center Name & PI:</b> SRIMSC; Hugh Rosen</p><p><b>Assay Submitter & Institution:</b> Claes Wahlestedt, The Scripps
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Research Institute (TSRI)</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
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<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1791" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1791</a></p><div id="ml075.s1"><h2 id="_ml075_s1_">Probe Structure & Characteristics</h2><p>Four different compounds are claimed as novel antagonist probes to the NPY-Y2
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receptor. These four probes demonstrate sub-micromolar affinity to the Y2 receptor,
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do not antagonize the Y1R receptor, and do not present significant cytotoxicity.
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Additionally, they are all blood-brain barrier penetrant. In this regard they all
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represent an improvement over the current NPY Y2 antagonist probe, BIIE 0246. The
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four probes are illustrated below:</p><div id="ml075.fu1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu1.jpg" alt="Scaffold 1 (Piperidine carbothioamide) [ML075]." /></div><h3><span class="title">Scaffold 1 (Piperidine carbothioamide) [ML075]</span></h3></div><div id="ml075.fu2" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu2.jpg" alt="Scaffold 2 (Arysulfamoyl benzamide) [ML074]." /></div><h3><span class="title">Scaffold 2 (Arysulfamoyl benzamide) [ML074]</span></h3></div><div id="ml075.fu3" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu3.jpg" alt="Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]." /></div><h3><span class="title">Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]</span></h3></div><div id="ml075.fu4" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu4.jpg" alt="Scaffold 4 (Dimethylisoxazole) [ML072]." /></div><h3><span class="title">Scaffold 4 (Dimethylisoxazole) [ML072]</span></h3></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075tu1"><a href="/books/NBK47354/table/ml075.tu1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml075tu1" rid-ob="figobml075tu1"><img class="small-thumb" src="/books/NBK47354/table/ml075.tu1/?report=thumb" src-large="/books/NBK47354/table/ml075.tu1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml075.tu1"><a href="/books/NBK47354/table/ml075.tu1/?report=objectonly" target="object" rid-ob="figobml075tu1">Table</a></h4></div></div></div><div id="ml075.s2"><h2 id="_ml075_s2_">Recommendations for the scientific use of this probe</h2><p>These probes are useful for assays aiming to block cellular NPY Y2 receptor (Y2R)
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signaling, leading to increased cAMP levels, without inhibiting NPY Y1 receptor
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(Y1R) activity. The representative (“best-in-class”)
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compounds from scaffold 1 (<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17507305</a></b>), scaffold 2
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(<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17413392</a></b>), scaffold 3 (<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-4242079</a></b>), and scaffold
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4 (<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-22413249</a></b>) displace agonist from the Y2R with high affinity. These
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probes bind to fewer off-target receptors than BIIE 0246, currently the most widely
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used Y2R antagonist. Most importantly, and in contrast to BIIE 0246, these
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best-in-class probes are brain penetrant and thus able to reach Y2R binding sites in
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both the periphery and brain. Additional information regarding the compounds and
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assays employed in this probe development campaign can be found in (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>).</p></div><div id="ml075.s3"><h2 id="_ml075_s3_">1. Scientific Rationale for Project</h2><p>Due to its expression profile and biological action, NPY Y2 is an attractive GPCR
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target for anxiolytic research. Additionally, Y2 is predicted to be a therapeutic
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target in alcoholism. It has been reported, however, that the complex structure and
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high molecular weight of BIIE 0246 (the current NPY Y2 antagonist) limit its
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usefulness as an <i>in vivo</i> pharmacological tool (<a class="bibr" href="#ml075.r2" rid="ml075.r2">2</a>). It is therefore necessary to produce brain penetrant,
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high affinity selective ligands for the Y2 receptor.</p></div><div id="ml075.s4"><h2 id="_ml075_s4_">2. Project Description</h2><div id="ml075.s2b"><h3>a. Information for each Assay Implemented and Screening Run</h3><div id="ml075.s2bi"><h4>i. PubChem Bioassay Name(s), AID(s), Assay-Type (Primary, DR, Counterscreen,
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Secondary)</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t1"><a href="/books/NBK47354/table/ml075.t1/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figml075t1" rid-ob="figobml075t1"><img class="small-thumb" src="/books/NBK47354/table/ml075.t1/?report=thumb" src-large="/books/NBK47354/table/ml075.t1/?report=previmg" alt="Table 2. PubChem BioAssay." /></a><div class="icnblk_cntnt"><h4 id="ml075.t1"><a href="/books/NBK47354/table/ml075.t1/?report=objectonly" target="object" rid-ob="figobml075t1">Table 2</a></h4><p class="float-caption no_bottom_margin">PubChem BioAssay. </p></div></div></div><div id="ml075.s6"><h4>ii. Assay Rationale & Description</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t2"><a href="/books/NBK47354/table/ml075.t2/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml075t2" rid-ob="figobml075t2"><img class="small-thumb" src="/books/NBK47354/table/ml075.t2/?report=thumb" src-large="/books/NBK47354/table/ml075.t2/?report=previmg" alt="Table 3. Assay Rationale and Description." /></a><div class="icnblk_cntnt"><h4 id="ml075.t2"><a href="/books/NBK47354/table/ml075.t2/?report=objectonly" target="object" rid-ob="figobml075t2">Table 3</a></h4><p class="float-caption no_bottom_margin">Assay Rationale and Description. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t3"><a href="/books/NBK47354/table/ml075.t3/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml075t3" rid-ob="figobml075t3"><img class="small-thumb" src="/books/NBK47354/table/ml075.t3/?report=thumb" src-large="/books/NBK47354/table/ml075.t3/?report=previmg" alt="Table 4. Reagents and Source." /></a><div class="icnblk_cntnt"><h4 id="ml075.t3"><a href="/books/NBK47354/table/ml075.t3/?report=objectonly" target="object" rid-ob="figobml075t3">Table 4</a></h4><p class="float-caption no_bottom_margin">Reagents and Source. </p></div></div></div><div id="ml075.s7"><h4>iii. Summary of Results</h4><p>Compared to previously described Y2R antagonists, the compounds described
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herein offer greater promise for elucidating the Y2R signaling pathway.</p></div></div><div id="ml075.s8"><h3>b. Probe Optimization</h3></div><div id="ml075.s9"><h3>i. Description of SAR & chemistry strategy (including structure and
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data) that led to the probe.</h3><p>Since receptor subtype selective antagonists were desired, compounds worth
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follow-up from the Primary, Confirmation and Counterscreening were required to
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exhibit an IC<sub>50</sub> value of less than 10 μM at Y2R and
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greater than 35 μM at Y1 in dose response assays. Structures and
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data for each probe can be found in the SAR tables. The chemistry strategy that
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lead to each scaffold is described below:</p><p><b>Scaffold 1:</b> Based on the above criteria, one compound belonging
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to the piperidine-carbothioamide scaffold was identified:
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17507305</a></b>. This compound does not share structural
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similarities with the known NPY-Y2 antagonist BIIE 0246 or JNJ-5207787.
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Analogs were purchased in powder form or reordered from the MLSMR in liquid
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form and tested in dose response assays against both receptors. Results for
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these analogs are summarized in the SAR table below.</p><p><b>Scaffold 2:</b> Based on the above criteria, a compound belonging to
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the arysulfamoyl benzamide scaffold was identified:
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17413392</a></b>. This compound does not share structural
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similarities with the known NPY-Y2 antagonist BIIE0246 or JNJ-5207787.
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Analogs were purchased in powder form or re-ordered from the MLSMR in liquid
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form and tested in dose response assays against both receptors. Results for
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these analogs are summarized in the SAR table below.</p><p><b>Scaffold 3:</b> Based on the above criteria, a compound belonging to
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the aryl-1,2,4-oxadiazole scaffold was identified: <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-4242079</a></b>.
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This compound does not share structural similarities with the known NPY-Y2
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antagonist BIIE0246 or JNJ-5207787. Analogs were purchased in powder form or
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re-ordered from the MLSMR in liquid form and tested in dose response assays
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against both receptors. Results for these analogs are summarized in the SAR
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table below.</p><p><b>Scaffold 4:</b> Based on the above criteria, a compound belonging to
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the dimethylisoxazole scaffold was identified: <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-22413249</a></b>.
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This compound does not share structural similarities with the known NPY-Y2
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antagonist BIIE0246 or JNJ-5207787. Analogs were purchased in powder form or
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re-ordered from the MLSMR in liquid form and tested in dose response assays
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against both receptors. Results for these analogs are summarized in the SAR
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table below.</p></div></div><div id="ml075.s10"><h2 id="_ml075_s10_">3. Probe</h2><div id="ml075.s11"><h3>a. Chemical name</h3><p><b>Scaffold 1:</b>
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N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-
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carbothioamide [<a href="/pcsubstance/?term=ML075[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML075</a>]</p><p><b>Scaffold 2:</b>
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4-chloro-3-[(2,5-dimethylphenyl)sulfamoyl]-N-(2-phenylphenyl)benzamide
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[<a href="/pcsubstance/?term=ML074[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML074</a>]</p><p><b>Scaffold 3:</b>
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2-(2-methoxyphenyl)-N-[4-[5-(3-methoxyphenyl)-1,2,
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4-oxadiazol-3-yl]phenyl]acetamide
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[<a href="/pcsubstance/?term=ML073[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML073</a>]</p><p><b>Scaffold 4:</b>
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3,5-dimethyl-4-[(4-methylphenyl)sulfonyl-phenylmethyl]-1,2-oxazole
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[<a href="/pcsubstance/?term=ML072[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML072</a>]</p></div><div id="ml075.s12"><h3>b. Probe chemical structure</h3><div id="ml075.fu6" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu1.jpg" alt="Scaffold 1 (Piperidine carbothioamide) [ML075]." /></div><h3><span class="title">Scaffold 1 (Piperidine carbothioamide) [ML075]</span></h3></div><div id="ml075.fu7" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu2.jpg" alt="Scaffold 2 (Arysulfamoyl benzamide) [ML074]." /></div><h3><span class="title">Scaffold 2 (Arysulfamoyl benzamide) [ML074]</span></h3></div><div id="ml075.fu8" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu3.jpg" alt="Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]." /></div><h3><span class="title">Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]</span></h3></div><div id="ml075.fu9" class="figure bk_fig"><div class="graphic"><img src="/books/NBK47354/bin/ml075fu4.jpg" alt="Scaffold 4 (Dimethylisoxazole) [ML072]." /></div><h3><span class="title">Scaffold 4 (Dimethylisoxazole) [ML072]</span></h3></div></div><div id="ml075.s13"><h3>c. Structural Verification Information of probe SID</h3><p>LCMS</p></div><div id="ml075.s14"><h3>d. PubChem CID (corresponding to the SID)</h3><p><b>Scaffold 1:</b> CID-2936384</p><p><b>Scaffold 2:</b> CID-2228302</p><p><b>Scaffold 3:</b> CID-3236979</p><p><b>Scaffold 4:</b> CID-4460128</p></div><div id="ml075.s15"><h3>e. Availabilty from vendor</h3><p><b>Scaffold 1:</b> Asinex, catalog number BAS 01915526</p><p><b>Scaffold 2:</b> ChemBridge, catalog number 7955494</p><p><b>Scaffold 3:</b> ChemDiv, catalog number K907-0250</p><p><b>Scaffold 4:</b> Specs, catalog number AM970/41069539</p></div><div id="ml075.s16"><h3>f. Mode of action for biological activity of probe</h3><p><b>Scaffold 1:</b> Using cell-based <sup>125</sup>I-PYY binding assays, the
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Assay Provider has determined that <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17507305</a></b> competes with
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agonist for binding to the NPY Y2 receptor. In cells expressing NPY Y2, this
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compound exhibited a K<sub>i</sub> value of 1.55 nM (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>). No significant blockade of <sup>125</sup>I-PYY
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binding in cells expressing NPY Y1 was detected, even at concentrations up to 50
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μM. These results suggest that this probe binds to the NPY Y2
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receptor and does not bind to the Y1 receptor subtype.</p><p><b>Scaffold 2:</b> Using cell-based <sup>125</sup>I-PYY binding assays, the
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Assay Provider has determined that <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17413392</a></b> competes with
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agonist for binding to the NPY Y2 receptor. In cells expressing NPY Y2, this
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compound exhibited a K<sub>i</sub> value of 1.93 nM (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>). No significant blockade of <sup>125</sup>I-PYY
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binding in cells expressing NPY Y1 was detected, even at concentrations up to 50
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μM. These results suggest that this probe binds to the NPY Y2
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receptor and does not bind to the Y1 receptor subtype.</p><p><b>Scaffold 3:</b> Using cell-based <sup>125</sup>I-PYY binding assays, the
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Assay Provider has determined that <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-4242079</a></b> competes with agonist
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for binding to the NPY Y2 receptor. In cells expressing NPY Y2, this compound
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exhibited a K<sub>i</sub> value of 6.0 nM (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>). No significant blockade of <sup>125</sup>I-PYY binding in cells
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expressing NPY Y1 was detected, even at concentrations up to 50 μM.
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These results suggest that this probe binds to the NPY Y2 receptor and does not
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bind to the Y1 receptor subtype.</p><p><b>Scaffold 4:</b> Using cell-based <sup>125</sup>I-PYY binding assays, the
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Assay Provider has determined that <b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-22413249</a></b> competes with
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agonist for binding to the NPY Y2 receptor. In cells expressing NPY Y2, this
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compound exhibited a K<sub>i</sub> value of 60.3 nM (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>). No significant blockade of <sup>125</sup>I-PYY
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binding in cells expressing NPY Y1 was detected, even at concentrations up to 50
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μM. These results suggest that this probe binds to the NPY Y2
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receptor and does not bind to the Y1 receptor subtype.</p></div><div id="ml075.s17"><h3>g. Detailed synthetic pathway for making probe</h3><p>Not applicable</p></div><div id="ml075.s18"><h3>h. Probe properties</h3><p><b>Scaffold 1:</b> Aqueous solubility, −8.47; ADMET BBB, 0.803;
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ADMET BBB level, 0; ADMET absorption level, 0; ADMET solubility,
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−5.463; ADMET solubility level, 2</p><p><b>Scaffold 2:</b> Aqueous solubility, −9.18; ADMET BBB, ND;
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ADMET BBB level, 4; ADMET absorption level, 2; ADMET solubility,
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−7.195; ADMET solubility level, 1</p><p><b>Scaffold 3:</b> Aqueous solubility, −6.86; ADMET BBB,
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−.253; ADMET BBB level, 2; ADMET absorption level, 0; ADMET
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solubility, −4.849; ADMET solubility level, 2</p><p><b>Scaffold 4:</b> Aqueous solubility, −6.11; ADMET BBB, .133;
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ADMET BBB level, 1; ADMET absorption level, 0; ADMET solubility,
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−5.237; ADMET solubility level, 2</p></div><div id="ml075.s19"><h3>i. A tabular presentation summarizing known probe properties</h3><p>Please see Tables of <a class="figpopup" href="/books/NBK47354/table/ml075.t4/?report=objectonly" target="object" rid-figpopup="figml075t4" rid-ob="figobml075t4">Probe
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Properties</a> and <a class="figpopup" href="/books/NBK47354/table/ml075.t5/?report=objectonly" target="object" rid-figpopup="figml075t5" rid-ob="figobml075t5">Probe Names</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t4"><a href="/books/NBK47354/table/ml075.t4/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figml075t4" rid-ob="figobml075t4"><img class="small-thumb" src="/books/NBK47354/table/ml075.t4/?report=thumb" src-large="/books/NBK47354/table/ml075.t4/?report=previmg" alt="Table 5. Probe Properties." /></a><div class="icnblk_cntnt"><h4 id="ml075.t4"><a href="/books/NBK47354/table/ml075.t4/?report=objectonly" target="object" rid-ob="figobml075t4">Table 5</a></h4><p class="float-caption no_bottom_margin">Probe Properties. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t5"><a href="/books/NBK47354/table/ml075.t5/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figml075t5" rid-ob="figobml075t5"><img class="small-thumb" src="/books/NBK47354/table/ml075.t5/?report=thumb" src-large="/books/NBK47354/table/ml075.t5/?report=previmg" alt="Table 6. Probe Names." /></a><div class="icnblk_cntnt"><h4 id="ml075.t5"><a href="/books/NBK47354/table/ml075.t5/?report=objectonly" target="object" rid-ob="figobml075t5">Table 6</a></h4><p class="float-caption no_bottom_margin">Probe Names. </p></div></div></div></div><div id="ml075.s20"><h2 id="_ml075_s20_">4. Appendices</h2><ol class="lower-alpha"><li class="half_rhythm"><div>
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<b>Comparative data on (<a class="bibr" href="#ml075.r1" rid="ml075.r1">1</a>)
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probes, (<a class="bibr" href="#ml075.r2" rid="ml075.r2">2</a>) similar compound
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structures (establishing SAR) and (<a class="bibr" href="#ml075.r3" rid="ml075.r3">3</a>) prior probes</b>
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</div></li><li class="half_rhythm"><div>
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<b>Comparative data showing probe specificity for target</b>
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</div></li></ol><p>See Tables <a class="figpopup" href="/books/NBK47354/table/ml075.t6/?report=objectonly" target="object" rid-figpopup="figml075t6" rid-ob="figobml075t6">7a</a>-<a class="figpopup" href="/books/NBK47354/table/ml075.t9/?report=objectonly" target="object" rid-figpopup="figml075t9" rid-ob="figobml075t9">d</a></p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t6"><a href="/books/NBK47354/table/ml075.t6/?report=objectonly" target="object" title="Table 7(a)" class="img_link icnblk_img figpopup" rid-figpopup="figml075t6" rid-ob="figobml075t6"><img class="small-thumb" src="/books/NBK47354/table/ml075.t6/?report=thumb" src-large="/books/NBK47354/table/ml075.t6/?report=previmg" alt="Table 7(a). SAR Scaffold 1: Piperidine-carbothioamide." /></a><div class="icnblk_cntnt"><h4 id="ml075.t6"><a href="/books/NBK47354/table/ml075.t6/?report=objectonly" target="object" rid-ob="figobml075t6">Table 7(a)</a></h4><p class="float-caption no_bottom_margin">SAR Scaffold 1: Piperidine-carbothioamide. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t7"><a href="/books/NBK47354/table/ml075.t7/?report=objectonly" target="object" title="Table 7(b)" class="img_link icnblk_img figpopup" rid-figpopup="figml075t7" rid-ob="figobml075t7"><img class="small-thumb" src="/books/NBK47354/table/ml075.t7/?report=thumb" src-large="/books/NBK47354/table/ml075.t7/?report=previmg" alt="Table 7(b). SAR Scaffold 2: Arylsulfamoylbenzamide." /></a><div class="icnblk_cntnt"><h4 id="ml075.t7"><a href="/books/NBK47354/table/ml075.t7/?report=objectonly" target="object" rid-ob="figobml075t7">Table 7(b)</a></h4><p class="float-caption no_bottom_margin">SAR Scaffold 2: Arylsulfamoylbenzamide. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t8"><a href="/books/NBK47354/table/ml075.t8/?report=objectonly" target="object" title="Table 7(c)" class="img_link icnblk_img figpopup" rid-figpopup="figml075t8" rid-ob="figobml075t8"><img class="small-thumb" src="/books/NBK47354/table/ml075.t8/?report=thumb" src-large="/books/NBK47354/table/ml075.t8/?report=previmg" alt="Table 7(c). SAR Scaffold 3: Aryl-1,2,4-oxadiazole." /></a><div class="icnblk_cntnt"><h4 id="ml075.t8"><a href="/books/NBK47354/table/ml075.t8/?report=objectonly" target="object" rid-ob="figobml075t8">Table 7(c)</a></h4><p class="float-caption no_bottom_margin">SAR Scaffold 3: Aryl-1,2,4-oxadiazole. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075t9"><a href="/books/NBK47354/table/ml075.t9/?report=objectonly" target="object" title="Table 7(d)" class="img_link icnblk_img figpopup" rid-figpopup="figml075t9" rid-ob="figobml075t9"><img class="small-thumb" src="/books/NBK47354/table/ml075.t9/?report=thumb" src-large="/books/NBK47354/table/ml075.t9/?report=previmg" alt="Table 7(d). SAR Scaffold 4: Dimethylisoxazole." /></a><div class="icnblk_cntnt"><h4 id="ml075.t9"><a href="/books/NBK47354/table/ml075.t9/?report=objectonly" target="object" rid-ob="figobml075t9">Table 7(d)</a></h4><p class="float-caption no_bottom_margin">SAR Scaffold 4: Dimethylisoxazole. </p></div></div></div><div id="ml075.bib"><h2 id="_ml075_bib_">5. Bibliography</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ml075.r1">Saldanha SA, Brothers SP, Spicer T, Cameron M, Mercer BA, Chase P, McDonald P, Wahlestedt C, Hodder PS. Selective and Brain Penetrant Neuropeptide Y Y2 Receptor
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Antagonists Discovered through Whole-Cell High Throughput
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Screening. <span></span> Submitted. [<a href="/pmc/articles/PMC2802430/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2802430</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19837904" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19837904</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ml075.r2">Bonaventure P, Nepomuceno D, Mazur C, Lord B, Rudolph DA, Jablonowski JA, Carruthers NI, Lovenberg TW. Characterization of
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N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(3-cyanophenyl)-N-[1-(2-cyclopentyl-ethyl)-piperidin-4yl]acrylamide
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(JNJ-5207787), a small molecule antagonist of the neuropeptide Y Y 2
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receptor. <span><span class="ref-journal">J Pharmacol Exp Ther. </span>2004 Mar;<span class="ref-vol">308</span>(3:):1130–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14617685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14617685</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ml075.r3">Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. Estimation of aqueous solubility of chemical compounds using
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E-state indices. <span><span class="ref-journal">J Chem Inf Comput Sci. </span>2001;<span class="ref-vol">41</span>:1488–1493.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11749573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11749573</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ml075.r4">Egan WJ, Merz KM Jr, Baldwin JJ. Prediction of drug absorption using multivariate
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statistics. <span><span class="ref-journal">J Med Chem. </span>2000;<span class="ref-vol">43</span>:3867–3877.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11052792" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11052792</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ml075.r5">Egan WJ, Lauri G. Prediction of intestinal permeability. <span><span class="ref-journal">Adv Drug Deliv Rev. </span>2002;<span class="ref-vol">54</span>:273–289.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11922948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11922948</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ml075.r6">Cheng A, Merz KM Jr. Prediction of aqueous solubility of a diverse set of
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compounds using quantitative structure-property
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relationships. <span><span class="ref-journal">J Med Chem. </span>2003;<span class="ref-vol">46</span>:3572–3580.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12904062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12904062</span></a>]</div></dd></dl></dl></div><div id="ml075.s21"><h2 id="_ml075_s21_">Brain Penetrance Data</h2><p>In order to determine whether the identified Y2R antagonists were brain-penetrant,
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selected compounds were injected intraperitoneally into adult mice at 10 mg/kg and
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levels in the brain tissue and plasma were measured after thirty minutes. BIIE 0246,
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the current NPY Y2 antagonist probe, exhibited poor penetration (only 2%
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of plasma levels). All probes demonstrated a higher brain penetrance than BIIE
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0246.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml075tu2"><a href="/books/NBK47354/table/ml075.tu2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figml075tu2" rid-ob="figobml075tu2"><img class="small-thumb" src="/books/NBK47354/table/ml075.tu2/?report=thumb" src-large="/books/NBK47354/table/ml075.tu2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ml075.tu2"><a href="/books/NBK47354/table/ml075.tu2/?report=objectonly" target="object" rid-ob="figobml075tu2">Table</a></h4></div></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK47354_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">SA Saldanha</span>, <span itemprop="author">SP Brothers</span>, <span itemprop="author">T Spicer</span>, <span itemprop="author">M Cameron</span>, <span itemprop="author">BA Mercer</span>, <span itemprop="author">P Chase</span>, <span itemprop="author">P McDonald</span>, <span itemprop="author">C Wahlestedt</span>, and <span itemprop="author">PS Hodder</span>.</p><h3>Publication History</h3><p class="small">Received: <span itemprop="datePublished">January 13, 2009</span>; Last Update: <span itemprop="dateModified">August 6, 2010</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p>National Center for Biotechnology Information (US), Bethesda (MD)</p><h3>NLM Citation</h3><p>Saldanha SA, Brothers SP, Spicer T, et al. Probe Report for NPY-Y2 Receptor Antagonists. 2009 Jan 13 [Updated 2010 Aug 6]. 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/ml076/?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/ml071/?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="figobml075fu1"><div id="ml075.fu1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu1.jpg" alt="Scaffold 1 (Piperidine carbothioamide) [ML075]." /></div><h3><span class="title">Scaffold 1 (Piperidine carbothioamide) [ML075]</span></h3></div></article><article data-type="fig" id="figobml075fu2"><div id="ml075.fu2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu2.jpg" alt="Scaffold 2 (Arysulfamoyl benzamide) [ML074]." /></div><h3><span class="title">Scaffold 2 (Arysulfamoyl benzamide) [ML074]</span></h3></div></article><article data-type="fig" id="figobml075fu3"><div id="ml075.fu3" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu3.jpg" alt="Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]." /></div><h3><span class="title">Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]</span></h3></div></article><article data-type="fig" id="figobml075fu4"><div id="ml075.fu4" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu4.jpg" alt="Scaffold 4 (Dimethylisoxazole) [ML072]." /></div><h3><span class="title">Scaffold 4 (Dimethylisoxazole) [ML072]</span></h3></div></article><article data-type="table-wrap" id="figobml075tu1"><div id="ml075.tu1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.tu1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.tu1_lrgtbl__"><table><thead><tr><th id="hd_h_ml075.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Scaffold ID</th><th id="hd_h_ml075.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Scaffold Name</th><th id="hd_h_ml075.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID/ML</th><th id="hd_h_ml075.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th id="hd_h_ml075.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target (NPY Y2) IC<sub>50</sub>
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(μM)</th><th id="hd_h_ml075.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti-Target (NPY Y1) IC<sub>50</sub>
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(μM)</th><th id="hd_h_ml075.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Secondary Assay CC<sub>50</sub>
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(μM)</th><th id="hd_h_ml075.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Brain Penetrance (ng/mL)</th></tr></thead><tbody><tr><td headers="hd_h_ml075.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</td><td headers="hd_h_ml075.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Piperidine carbothioamide</td><td headers="hd_h_ml075.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2936384/<a href="/pcsubstance/?term=ML075[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML075</a></td><td headers="hd_h_ml075.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17507305</a></td><td headers="hd_h_ml075.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.220
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[<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1272</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35
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[<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1279</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">74</td><td headers="hd_h_ml075.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1656 ± 749</td></tr><tr><td headers="hd_h_ml075.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</td><td headers="hd_h_ml075.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Arysulfamoylbenzamide</td><td headers="hd_h_ml075.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2228302/<a href="/pcsubstance/?term=ML074[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML074</a></td><td headers="hd_h_ml075.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17413392</a></td><td headers="hd_h_ml075.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.428
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[<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1272</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4
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[<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1279</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">20.6</td><td headers="hd_h_ml075.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">395 ± 16</td></tr><tr><td headers="hd_h_ml075.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</td><td headers="hd_h_ml075.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Aryl-1,2,4-oxadiazole</td><td headers="hd_h_ml075.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3236979/<a href="/pcsubstance/?term=ML073[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML073</a></td><td headers="hd_h_ml075.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">4242079</a></td><td headers="hd_h_ml075.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.733 [<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1272</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35 [<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1279</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1860 ± 135</td></tr><tr><td headers="hd_h_ml075.tu1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</td><td headers="hd_h_ml075.tu1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dimethylisoxazole</td><td headers="hd_h_ml075.tu1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4460128/<a href="/pcsubstance/?term=ML072[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML072</a></td><td headers="hd_h_ml075.tu1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">22413249</a></td><td headers="hd_h_ml075.tu1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.917 [<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1272</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4 [<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1279</a>]</td><td headers="hd_h_ml075.tu1_1_1_1_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.tu1_1_1_1_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">513 ± 57</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t1"><div id="ml075.t1" class="table"><h3><span class="label">Table 2</span><span class="title">PubChem BioAssay</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t1_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AID</th><th id="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Name</th><th id="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Assay Type</th><th id="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target</th><th id="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Powder Sample</th><th id="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Compound Concentration</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">793</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary cell based
|
|
high-throughput screening assay for antagonists of
|
|
neuropeptide Y receptor Y2.</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary Assay (1X
|
|
%INH)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y2</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1256" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1256</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Counterscreen assay for
|
|
antagonists of neuropeptide Y receptor Y2 (NPY-Y2):
|
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Cell-based high throughput assay to measure NPY-Y1
|
|
antagonism.</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Counterscreen Assay (3X
|
|
%INH)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y1</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.6 μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1257</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cell-based high throughput
|
|
confirmation assay for antagonists of neuropeptide Y
|
|
receptor.</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Confirmation Assay (3X
|
|
%INH)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y2</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.7 μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1272</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dose response cell-based
|
|
screening assay for antagonists of neuropeptide Y receptor
|
|
Y2.</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dose Response (3X
|
|
IC<sub>50</sub>)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y2</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10-point, 1:3 dilution
|
|
starting at 35 μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1040" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1040</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primary cell-based
|
|
high-throughput screening assay for antagonists of
|
|
NPY-Y1</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Primary Assay (1X
|
|
%INH)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y1</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.6 μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1279</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dose response counterscreen for
|
|
neuropeptide Y receptor Y2 (NPY-Y2): Cell-based high
|
|
throughput assay to measure NPY-Y1 antagonism.</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Dose Response Counterscreen
|
|
(3X IC<sub>50</sub>)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y1</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10-point, 1:3 dilution
|
|
starting at 35 μM</td></tr><tr><td headers="hd_h_ml075.t1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2142</a></td><td headers="hd_h_ml075.t1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Late stage results from the
|
|
probe development effort to identify antagonists of
|
|
neuropeptide Y receptor Y2 (NPY-Y2)</td><td headers="hd_h_ml075.t1_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Various (Cytotoxicity and
|
|
Brain Penetrance assays)</td><td headers="hd_h_ml075.t1_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">NPY-Y2</td><td headers="hd_h_ml075.t1_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Yes</td><td headers="hd_h_ml075.t1_1_1_1_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Various</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t2"><div id="ml075.t2" class="table"><h3><span class="label">Table 3</span><span class="title">Assay Rationale and Description</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t2_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">AID</th><th id="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay Rationale</th><th id="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Assay Description</th><th id="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Z′</th><th id="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">S:B</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">793</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine the ability of test compounds to inhibit NPY Y2
|
|
activity.</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">In this assay test compounds are
|
|
screened for their ability to increase agonist-mediated cAMP
|
|
levels in a cell line transfected with the NPY-Y2 receptor
|
|
and a cyclic-nucleotide gated channel (CNG). The cells are
|
|
treated with isoproterenol to activate adenylate cyclase and
|
|
open the CNG channel, leading to a change in membrane
|
|
potential that is measured using a fluorescent probe. The
|
|
addition of the agonist NPY peptide counteracts cAMP
|
|
accumulation induced by isoproterenol. As designed, test
|
|
compounds that act as NPY-Y2 receptor antagonists will
|
|
reverse the reduction in well fluorescence.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.78+/− 0.04</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.09
|
|
+/− 0.33</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1256" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1256</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine the ability of test compounds to inhibit NPY Y1
|
|
activity.</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Same as <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-793</a>, except that
|
|
test compounds are tested in triplicate and are incubated
|
|
with a cell line that is transfected with the NPY-Y1
|
|
receptor.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.79
|
|
+/− 0.01</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.28
|
|
+/− 0.04</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1257</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
confirm activity of compounds previously identified as
|
|
active in a previous set of experiments (PubChem AID
|
|
793).</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Same as <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-793</a>, except that
|
|
compounds are tested in triplicate..</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.81+/− 0.02</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.99
|
|
+/− 0.13</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1272</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine dose response curves for compounds identified as
|
|
active in a previous set of experiments entitled, "Primary
|
|
cell-based high-throughput screening assay for antagonists
|
|
of neuropeptide Y receptor Y2 (NPY-Y2)," (PubChem AID
|
|
793).</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Same as <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-793</a>, except that
|
|
test compounds were assayed in triplicate in a 10-point, 1:3
|
|
dilution series starting at a nominal test concentration of
|
|
35 μM.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.84
|
|
+/− 0.02</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.04
|
|
+/− 0.19</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1040" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1040</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine the ability of test compounds to inhibit NPY Y1
|
|
activity.</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Same as <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1256" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1256</a>, except that
|
|
test compounds are incubated with a cell line that is
|
|
transfected with the NPY-Y1 receptor.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.65+/− 0.06</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.35
|
|
+/− 0.28</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1279</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine whether compounds identified as active in a
|
|
previous set of experiments (PubChem <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-793</a>) were
|
|
nonselective due to inhibition of the NPY Y1 receptor.</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Same as <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">AID-1272</a>, except that
|
|
test compounds are incubated with a cell line that is
|
|
transfected with the NPY-Y1 receptor.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.70+/− 0.10</td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.56+/−0.09</td></tr><tr><td headers="hd_h_ml075.t2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2142</a></td><td headers="hd_h_ml075.t2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine whether probe candidates were cytotoxic and brain
|
|
penetrant.</td><td headers="hd_h_ml075.t2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The purpose of this assay is to
|
|
determine whether compounds of interest reduce cell
|
|
viability. Y2R HEK293-CNG cells were seeded at 500 cells per
|
|
well in 1536-well plates in 5 uL growth media. Compounds (in
|
|
DMSO) were prepared as 10-point, 1:3 serial dilutions
|
|
starting at 11 µM final concentration were added to cells.
|
|
Plates were incubated for 24, 48 or 72 h at 37 C. After
|
|
incubation, 5 uL of CellTiter-Glo (Promega, Madison, WI)
|
|
were added to each well and the plates were allowed to
|
|
incubate for 15 min at room temperature. Luminescence was
|
|
then measured (ViewLux plate reader, PerkinElmer, Turku,
|
|
Finland). Viability was measured as a percentage relative to
|
|
control cells treated with DMSO alone (0%
|
|
cytotoxicity) and cells treated with 100 µM Doxorubicin
|
|
(100% cytotoxicity).<br /><br />Plasma and
|
|
brain levels of the compounds were assessed in C57Bl6 mice
|
|
30 minutes after dosing 10 mg/kg intraperitoneally. Samples
|
|
were formulated at 2 mg/mL in 10/10/80 DMSO/tween/water.
|
|
Blood was collected into EDTA containing tubes at 30 min and
|
|
plasma was generated using standard centrifugation
|
|
techniques. Brain samples were frozen upon collection and
|
|
all samples were stored at −80 C until analyzed.
|
|
Brain tissue was not perfused prior to freezing to prevent
|
|
diffusion of the compound out of the tissue during the
|
|
process. Plasma samples were analyzed by treating 25
|
|
μL of plasma with 125 μL of
|
|
acetonitrile containing an internal standard (propanolol)
|
|
and filtering through a Millipore Multiscreen Solvinter 0.45
|
|
μm low binding PTFE hydrophilic filter. The
|
|
filtrate was analyzed by LC- MS/MS using an API Sciex 4000.
|
|
MRM methods were developed in positive ion mode and
|
|
concentrations were determined using a standard curve
|
|
between 2 to 2000 ng/mL. Samples with concentrations outside
|
|
of the curve were diluted with blank plasma and reanalyzed.
|
|
Similar conditions were used to determine brain levels
|
|
except the samples were weighed and acetonitrile was added
|
|
(10x, weight by volume). The samples were sonicated to
|
|
extract the compound from the brain matrix and then filtered
|
|
as described above. A density of 1 g/mL was used to convert
|
|
compound per mg tissue into molar equivalents.</td><td headers="hd_h_ml075.t2_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td><td headers="hd_h_ml075.t2_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t3"><div id="ml075.t3" class="table"><h3><span class="label">Table 4</span><span class="title">Reagents and Source</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t3_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AID</th><th id="hd_h_ml075.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Reagent (Source)</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t3_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/793" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">793</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1256" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1256</a>, <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1257" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1257</a>, and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1272</a></b>
|
|
</td><td headers="hd_h_ml075.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropeptide Y receptor Y2
|
|
HEK293-CNG cells (BD Biosciences, part 344870)<br /> 10x
|
|
ACTOne Membrane Potential Assay Kit (BD Biosciences, part
|
|
<a href="/nuccore/92255785" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">BD354663</a>)<br /> Phosphate Buffered Saline (Invitrogen,
|
|
part 10010-023)<br /> DMEM (Invitrogen, part
|
|
11965-092)<br /> Fetal Bovine Serum (Invitrogen, part
|
|
16140-071)<br /> Trypsin-EDTA solution (Invitrogen, part
|
|
25200-056)<br /> Geneticin (Invitrogen, part
|
|
10131-027)<br /> Puromycin (Sigma, part P9620)<br />
|
|
Isoproterenol (Sigma, part I6504)<br /> Ro 20-1724 (Sigma,
|
|
part B8279)<br /> Neuropeptide Y (American Peptide, part
|
|
60-1-11B)<br /> BIIE 0246 (Tocris, part 1700)<br />
|
|
1536-well plates (Greiner, part 789072)<br /> T-175 tissue
|
|
culture flasks (Corning, part 431)</td></tr><tr><td headers="hd_h_ml075.t3_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/1040" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1040</a> and <a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/1279" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">1279</a></b>
|
|
</td><td headers="hd_h_ml075.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As above, with the
|
|
following changes: Neuropeptide Y receptor
|
|
Y1 HEK293-CNG cells (BD Biosciences, part 344869) (replaces
|
|
Y2 cells)</td></tr><tr><td headers="hd_h_ml075.t3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2142" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2142</a></td><td headers="hd_h_ml075.t3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Y2R HEK293-CNG cells ;
|
|
CellTiter-Glo (Promega, Madison, WI); DMSO; Doxorubicin
|
|
DMSO/tween/water; EDTA; acetonitrile containing an internal
|
|
standard (propanolol)</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobml075fu6"><div id="ml075.fu6" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu1.jpg" alt="Scaffold 1 (Piperidine carbothioamide) [ML075]." /></div><h3><span class="title">Scaffold 1 (Piperidine carbothioamide) [ML075]</span></h3></div></article><article data-type="fig" id="figobml075fu7"><div id="ml075.fu7" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu2.jpg" alt="Scaffold 2 (Arysulfamoyl benzamide) [ML074]." /></div><h3><span class="title">Scaffold 2 (Arysulfamoyl benzamide) [ML074]</span></h3></div></article><article data-type="fig" id="figobml075fu8"><div id="ml075.fu8" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu3.jpg" alt="Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]." /></div><h3><span class="title">Scaffold 3 (Aryl-1,2,4-oxadiazole) [ML073]</span></h3></div></article><article data-type="fig" id="figobml075fu9"><div id="ml075.fu9" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK47354/bin/ml075fu4.jpg" alt="Scaffold 4 (Dimethylisoxazole) [ML072]." /></div><h3><span class="title">Scaffold 4 (Dimethylisoxazole) [ML072]</span></h3></div></article><article data-type="table-wrap" id="figobml075t4"><div id="ml075.t4" class="table"><h3><span class="label">Table 5</span><span class="title">Probe Properties</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t4_lrgtbl__"><table class="no_margin"><thead><tr><th id="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Scaffold:</th><th id="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1</th><th id="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2</th><th id="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3</th><th id="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>CID</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2936384</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2228302</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3236979</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4460128</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>SID</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17507305</a></td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17413392</a></td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">4242079</a></td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">22413249</a></td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>ML#</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML075[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML075</a></td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML074[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML074</a></td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML073[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML073</a></td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;"><a href="/pcsubstance/?term=ML072[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML072</a></td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>MLS</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS000569101</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS000581978</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS000047258</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MLS000698406</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>MF</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">C<sub>27</sub>H<sub>30</sub>N<sub>2</sub>O<sub>2</sub>S</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">C<sub>27</sub>H<sub>23</sub>ClN<sub>2</sub>O<sub>3</sub>S</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">C<sub>24</sub>H<sub>21</sub>N<sub>3</sub>O<sub>4</sub></td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">C<sub>19</sub>H<sub>19</sub>NO<sub>3</sub>S</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>MW</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">446.6043</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">491.00112</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">415.4412</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">341.4240</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Formal Charge</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>H Acceptor</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>H Donor</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Atom Count</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">32</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">34</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">31</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">24</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Rotatable Bonds</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Rings</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Stereoatoms</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>AlogP</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.443</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.257</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.931</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.92</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>logD</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">5.99</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">6.257</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.931</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.92</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Topological Polar Surface Area</b>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44.7</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">75.3</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">86.48</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">60.2</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Aqueous solubility</b>
|
|
<sup>a</sup>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−8.47</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−9.18</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−6.86</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−6.11</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>ADMET BBB</b>
|
|
<sup>b</sup>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.803</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ND</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−.253</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">.133</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>ADMET BBB level</b>
|
|
<sup>c</sup>
|
|
</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>ADMET absorption level</b>
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<sup>d</sup>
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</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>ADMET solubility</b>
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<sup>e</sup>
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</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−5.463</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−7.195</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−4.849</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">−5.237</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>ADMETT solubility level</b>
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<sup>f</sup>
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</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Vendor</b>
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</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Asinex</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ChemBridge</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">ChemDiv</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">Specs</td></tr><tr><td headers="hd_h_ml075.t4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Vendor Catalog Number</b>
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</td><td headers="hd_h_ml075.t4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">BAS 01915526</td><td headers="hd_h_ml075.t4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">7955494</td><td headers="hd_h_ml075.t4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">K907-0250</td><td headers="hd_h_ml075.t4_1_1_1_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">AM970/41069539</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="ml075.tfn1"><p class="no_margin">Aqueous solubility is expressed as logS, where S is solubility in
|
|
mol/L. The method used is the multiple linear regression model based
|
|
on Electrotopological State indices published in (<a class="bibr" href="#ml075.r2" rid="ml075.r2">2</a>).</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="ml075.tfn2"><p class="no_margin">ADMET_BBB: Log of Brain/Blood partition coefficient (LogBB). See
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(<a class="bibr" href="#ml075.r4" rid="ml075.r4">4</a>) for details on
|
|
this method.</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="ml075.tfn3"><p class="no_margin">ADMET_BBB_Level: Ranking of the LogBB values into one of the
|
|
following levels (see (<a class="bibr" href="#ml075.r4" rid="ml075.r4">4</a>, <a class="bibr" href="#ml075.r5" rid="ml075.r5">5</a>) for
|
|
details): 0: Very High 1: High 2: Medium 3: Low 4: Undefined
|
|
(molecule is outside the confidence area of the regression
|
|
model).</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="ml075.tfn4"><p class="no_margin">ADMET Passive Intestinal Absorption properties. A ranking of the
|
|
molecule into one of the following levels (see (<a class="bibr" href="#ml075.r4" rid="ml075.r4">4</a>, <a class="bibr" href="#ml075.r5" rid="ml075.r5">5</a>) for details): 0: Good 1: Moderate 2: Poor 3: Very
|
|
Poor</p></div></dd></dl><dl class="bkr_refwrap"><dt>e</dt><dd><div id="ml075.tfn5"><p class="no_margin">ADMET_Solubility: Log of the water solubility at 25 degrees, LogSw,
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|
in mol/L. See (<a class="bibr" href="#ml075.r6" rid="ml075.r6">6</a>) for
|
|
more information.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobml075t5"><div id="ml075.t5" class="table"><h3><span class="label">Table 6</span><span class="title">Probe Names</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t5_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Scaffold</th><th id="hd_h_ml075.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Probe CID</th><th id="hd_h_ml075.t5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Probe SID</th><th id="hd_h_ml075.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:bottom;">Probe Name (IUPAC)</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<b>1</b>
|
|
</td><td headers="hd_h_ml075.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2936384</td><td headers="hd_h_ml075.t5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17507305</a></td><td headers="hd_h_ml075.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-(4-ethoxyphenyl)-4-[hydroxy-di(phenyl)methyl]piperidine-1-carbothioamide
|
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[<a href="/pcsubstance/?term=ML075[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML075</a>]</td></tr><tr><td headers="hd_h_ml075.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>2</b>
|
|
</td><td headers="hd_h_ml075.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2228302</td><td headers="hd_h_ml075.t5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">17413392</a></td><td headers="hd_h_ml075.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4-chloro-3-[(2,5-dimethylphenyl)sulfamoyl]-N-(2-phenyl
|
|
phenyl) benzamide [<a href="/pcsubstance/?term=ML074[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML074</a>]</td></tr><tr><td headers="hd_h_ml075.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<b>3</b>
|
|
</td><td headers="hd_h_ml075.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3236979</td><td headers="hd_h_ml075.t5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">4242079</a></td><td headers="hd_h_ml075.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2-(2-methoxyphenyl)-N-[4-[5-(3-methoxyphenyl)-1,2,4-oxadiazol-3-
|
|
yl]phenyl]acetamide[<a href="/pcsubstance/?term=ML073[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML073</a>]</td></tr><tr><td headers="hd_h_ml075.t5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>4</b>
|
|
</td><td headers="hd_h_ml075.t5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4460128</td><td headers="hd_h_ml075.t5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;"><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">22413249</a></td><td headers="hd_h_ml075.t5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3,5-dimethyl-4-[(4-methylphenyl)sulfonyl-phenylmethyl]-1,2-oxazole
|
|
[<a href="/pcsubstance/?term=ML072[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML072</a>]</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t6"><div id="ml075.t6" class="table"><h3><span class="label">Table 7(a)</span><span class="title">SAR Scaffold 1: Piperidine-carbothioamide</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t6_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t6_1_1_1_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu10.jpg" alt="Image ml075fu10.jpg" /></div>
|
|
</th></tr><tr><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Vendor</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Catalog ID</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target: NPY-Y2 IC<sub>50</sub>
|
|
(μM)</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti- Target: NPY-Y1 IC<sub>50</sub>
|
|
(μM)</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CC<sub>50</sub> (μM)</th><th headers="hd_h_ml075.t6_1_1_1_1" id="hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Brain Penetrance</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu11.jpg" alt="Image ml075fu11.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17507305</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2936384</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000569101</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Asinex</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BAS 01915526</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.20E-07</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">74</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1656 ± 749 ng/mL</td></tr><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu12.jpg" alt="Image ml075fu12.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17431723</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2936750</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000552281</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Asinex</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">BAS 01915519</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.59E-06</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu13.jpg" alt="Image ml075fu13.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">56365809</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1261254</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-002454455</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7357839</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.83E-06</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>59.6</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu14.jpg" alt="Image ml075fu14.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17433143</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2945630</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000579559</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7653223</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.26E-05</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu15.jpg" alt="Image ml075fu15.jpg" /></div>
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</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17505667</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3649536</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000331483</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">InterBio Screen</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">STOCK4S-45177</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.42E-05</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu16.jpg" alt="Image ml075fu16.jpg" /></div>
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</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">56365810</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1934050</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-002454456</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7353950</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">60.1</td><td headers="hd_h_ml075.t6_1_1_1_1 hd_h_ml075.t6_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t7"><div id="ml075.t7" class="table"><h3><span class="label">Table 7(b)</span><span class="title">SAR Scaffold 2: Arylsulfamoylbenzamide</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t7_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t7_1_1_1_1" colspan="12" rowspan="1" style="text-align:left;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu17.jpg" alt="Image ml075fu17.jpg" /></div>
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</th></tr><tr><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R3</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Vendor</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Catalog ID</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target: NPY-Y2 IC<sub>50</sub>
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(μM) or % Inhibition</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti- Target: NPY-Y1 IC<sub>50</sub>
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(μM) or % Inhibition</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CC<sub>50</sub> (μM)</th><th headers="hd_h_ml075.t7_1_1_1_1" id="hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Brain Penetrance</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu18.jpg" alt="Image ml075fu18.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17413392</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2228302</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000581978</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7955494</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.28E-07</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">20.6</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">395 ± 16 ng/mL</td></tr><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CH<sub>3</sub></td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu19.jpg" alt="Image ml075fu19.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17413034</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2223246</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000582311</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7930722</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.98E-07</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">67</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">805 ± 305 ng/mL</td></tr><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CH<sub>3</sub></td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu20.jpg" alt="Image ml075fu20.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">56365811</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2242162</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-002454457</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7989629</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.18E-06</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">36.7</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td></tr><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu21.jpg" alt="Image ml075fu21.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17412946</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2233210</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000582690</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7969716</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.58E-06</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35.4</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">77.3</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td></tr><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CH<sub>3</sub></td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu22.jpg" alt="Image ml075fu22.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17413562</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2229952</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000582081</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7962686</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">15.4% @ 2.8
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μM</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.7% @ 3.5
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μM</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td></tr><tr><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu23.jpg" alt="Image ml075fu23.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Cl</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu24.jpg" alt="Image ml075fu24.jpg" /></div>
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</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17413799</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2228493</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000581991</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7956409</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.6% @ 2.8
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μM</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.5% @ 3.5
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μM</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t7_1_1_1_1 hd_h_ml075.t7_1_1_2_12" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t8"><div id="ml075.t8" class="table"><h3><span class="label">Table 7(c)</span><span class="title">SAR Scaffold 3: Aryl-1,2,4-oxadiazole</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t8_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t8_1_1_1_1" colspan="11" rowspan="1" style="text-align:left;vertical-align:top;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu25.jpg" alt="Image ml075fu25.jpg" /></div>
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</th></tr><tr><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Vendor</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Catalog ID</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target: NPY-Y2 IC<sub>50</sub>
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(μM)</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti- Target: NPY-Y1 IC<sub>50</sub>
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(μM)</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CC<sub>50</sub> (μM)</th><th headers="hd_h_ml075.t8_1_1_1_1" id="hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Brain Penetrance</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu26.jpg" alt="Image ml075fu26.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu27.jpg" alt="Image ml075fu27.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4242079</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3236979</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000047258</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemDiv</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">K907-0250</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.733</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1860 ± 135 ng/mL</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu28.jpg" alt="Image ml075fu28.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu29.jpg" alt="Image ml075fu29.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4255014</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2202984</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000049615</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7770357</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.24</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu30.jpg" alt="Image ml075fu30.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu31.jpg" alt="Image ml075fu31.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14736723</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2201684</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000536402</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7759153</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.07</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">26</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu32.jpg" alt="Image ml075fu32.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu33.jpg" alt="Image ml075fu33.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4241999</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3236909</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000047247</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemDiv</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">K907-0086</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4.63</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>11.8</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu34.jpg" alt="Image ml075fu34.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu35.jpg" alt="Image ml075fu35.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">56365812</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1291267</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">None</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7748574</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">13.8</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">81</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu36.jpg" alt="Image ml075fu36.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu37.jpg" alt="Image ml075fu37.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">56365813</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1292769</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">None</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemBridge</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">7757524</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">34.4</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">30.5</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu38.jpg" alt="Image ml075fu38.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu39.jpg" alt="Image ml075fu39.jpg" /></div>
|
|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4246387</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3240741</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000047246</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemDiv</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">K907-0083</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">39</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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|
<div class="graphic"><img src="/books/NBK47354/bin/ml075fu40.jpg" alt="Image ml075fu40.jpg" /></div>
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|
</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu41.jpg" alt="Image ml075fu41.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4244380</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3238986</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000047248</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemDiv</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">K907-0094</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">68.6</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu42.jpg" alt="Image ml075fu42.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu43.jpg" alt="Image ml075fu43.jpg" /></div>
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</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">14731189</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3425642</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000521294</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">ChemDiv</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">K907-0080</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">23.7</td><td headers="hd_h_ml075.t8_1_1_1_1 hd_h_ml075.t8_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075t9"><div id="ml075.t9" class="table"><h3><span class="label">Table 7(d)</span><span class="title">SAR Scaffold 4: Dimethylisoxazole</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.t9/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.t9_lrgtbl__"><table class="no_top_margin"><thead><tr><th id="hd_h_ml075.t9_1_1_1_1" colspan="11" rowspan="1" style="text-align:left;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu44.jpg" alt="Image ml075fu44.jpg" /></div>
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</th></tr><tr><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R1</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">R2</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">SID</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CID</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Vendor</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Catalog ID</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Target: NPY-Y2 IC<sub>50</sub>
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(μM) or % Inhibition</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Anti- Target: NPY-Y1 IC<sub>50</sub>
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(μM) or % Inhibition</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">CC<sub>50</sub> (μM)</th><th headers="hd_h_ml075.t9_1_1_1_1" id="hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Brain Penetrance</th></tr></thead><tbody><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu45.jpg" alt="Image ml075fu45.jpg" /></div>
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</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">22413249</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4460128</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000698406</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Specs</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AM-970/41069539</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.92</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">513 ± 57 ng/mL</td></tr><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu46.jpg" alt="Image ml075fu46.jpg" /></div>
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</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">22413387</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3402760</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000698150</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Specs</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AM-970/41069493</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8.19</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>35</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">>99</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu47.jpg" alt="Image ml075fu47.jpg" /></div>
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</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17386121</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4685085</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000538224</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Specs</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">AM-970/41069552</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.4% @ 2.8
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μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0.7% @ 3.5
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μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu48.jpg" alt="Image ml075fu48.jpg" /></div>
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</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17410523</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1471864</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000326274</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Ambinter</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">11L-541S</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3.3% @ 2.8
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μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">10.8% @ 3.5
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μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">H</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<div class="graphic"><img src="/books/NBK47354/bin/ml075fu49.jpg" alt="Image ml075fu49.jpg" /></div>
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</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17410952</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1486788</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000326284</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Ambinter</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">8L-520S</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">5.7% @ 2.8
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|
μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">18.1% @ 3.5
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μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr><tr><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Phenyl</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">17386328</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">4386086</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">MLS-000324960</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Chem Spider</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">3587851</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">2.5% @ 2.8
|
|
μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">1.8% @ 3.5
|
|
μM</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not Tested</td><td headers="hd_h_ml075.t9_1_1_1_1 hd_h_ml075.t9_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Not tested</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobml075tu2"><div id="ml075.tu2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK47354/table/ml075.tu2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ml075.tu2_lrgtbl__"><table><thead><tr><th id="hd_h_ml075.tu2_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ml075.tu2_1_1_1_1" style="text-align:center;vertical-align:middle;">ID</th><th id="hd_h_ml075.tu2_1_1_1_2" colspan="3" rowspan="1" style="text-align:center;vertical-align:middle;">Brain Penetration
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Studies<span class="hr"></span></th></tr><tr><th headers="hd_h_ml075.tu2_1_1_1_2" id="hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Plasma Concentration
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(μM)</th><th headers="hd_h_ml075.tu2_1_1_1_2" id="hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Brain Concentration
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(μM)</th><th headers="hd_h_ml075.tu2_1_1_1_2" id="hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Ratio
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[B]/[P]
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(%)</th></tr></thead><tbody><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17507305" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17507305</a></b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">8.5 ± 3.3</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">3.7 ± 1.7</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44</td></tr><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413392" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17413392</a></b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.1 ± 0.1</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.4 ± 0.03</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">36</td></tr><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/17413034" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-17413034</a></b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.6 ± 0.6</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.7 ± 0.6</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">106</td></tr><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/4242079" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-4242079</a></b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">9.0 ± 0.7</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">4.5 ± 0.3</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50</td></tr><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b><a href="https://pubchem.ncbi.nlm.nih.gov/substance/22413249" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID-22413249</a></b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.3 ± 0.3</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.5 ± 0.2</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">115</td></tr><tr><td headers="hd_h_ml075.tu2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<b>BIIE-0246</b>
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</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12 ± 2</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.2 ± 0.1</td><td headers="hd_h_ml075.tu2_1_1_1_2 hd_h_ml075.tu2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">2</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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