490 lines
No EOL
93 KiB
HTML
490 lines
No EOL
93 KiB
HTML
<?xml version="1.0" encoding="utf-8"?>
|
||
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
|
||
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">
|
||
|
||
<head><meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
|
||
<!-- AppResources meta begin -->
|
||
<meta name="paf-app-resources" content="" />
|
||
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
||
|
||
<!-- AppResources meta end -->
|
||
|
||
<!-- TemplateResources meta begin -->
|
||
<meta name="paf_template" content="" />
|
||
|
||
<!-- TemplateResources meta end -->
|
||
|
||
<!-- Logger begin -->
|
||
<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK143562" /><meta name="ncbi_domain" content="mlprobe" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK143562/" /><meta name="ncbi_pagename" content="A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
||
<!-- Logger end -->
|
||
|
||
<title>A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf</title>
|
||
|
||
<!-- AppResources external_resources begin -->
|
||
<link rel="stylesheet" href="/core/jig/1.15.2/css/jig.min.css" /><script type="text/javascript" src="/core/jig/1.15.2/js/jig.min.js"></script>
|
||
|
||
<!-- AppResources external_resources end -->
|
||
|
||
<!-- Page meta begin -->
|
||
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="Probe Reports from the NIH Molecular Libraries Program [Internet]" /><meta name="citation_title" content="A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor" /><meta name="citation_publisher" content="National Center for Biotechnology Information (US)" /><meta name="citation_date" content="2013/03/07" /><meta name="citation_author" content="Santhi Ganji" /><meta name="citation_author" content="Jiwen Zou" /><meta name="citation_author" content="Brock Brown" /><meta name="citation_author" content="Ekaterina V. Bobkova" /><meta name="citation_author" content="Robert Ardecky" /><meta name="citation_author" content="Craig Rosenstein" /><meta name="citation_author" content="Ian Pass" /><meta name="citation_author" content="Russell Dahl" /><meta name="citation_author" content="Stefan Vasile" /><meta name="citation_author" content="Eduard Sergienko" /><meta name="citation_author" content="Shenghua Shi" /><meta name="citation_author" content="Derek Stonich" /><meta name="citation_author" content="Anton Cheltov" /><meta name="citation_author" content="Ying Su" /><meta name="citation_author" content="Arianna Mangravita-Novo" /><meta name="citation_author" content="Michael Vicchiarelli" /><meta name="citation_author" content="Danielle McAnally" /><meta name="citation_author" content="Sylvia Kim" /><meta name="citation_author" content="Hung Nguyen" /><meta name="citation_author" content="Tina Kiffer Moreira" /><meta name="citation_author" content="Layton H. Smith" /><meta name="citation_author" content="Fu-Yue Zeng" /><meta name="citation_author" content="Jena Diwan" /><meta name="citation_author" content="Thomas D.Y. Chung" /><meta name="citation_author" content="Anthony B. Pinkerton" /><meta name="citation_author" content="Jonathan Kaunitz" /><meta name="citation_author" content="José Luis Millán" /><meta name="citation_pmid" content="23762953" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK143562/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="National Center for Biotechnology Information (US)" /><meta name="DC.Contributor" content="Santhi Ganji" /><meta name="DC.Contributor" content="Jiwen Zou" /><meta name="DC.Contributor" content="Brock Brown" /><meta name="DC.Contributor" content="Ekaterina V. Bobkova" /><meta name="DC.Contributor" content="Robert Ardecky" /><meta name="DC.Contributor" content="Craig Rosenstein" /><meta name="DC.Contributor" content="Ian Pass" /><meta name="DC.Contributor" content="Russell Dahl" /><meta name="DC.Contributor" content="Stefan Vasile" /><meta name="DC.Contributor" content="Eduard Sergienko" /><meta name="DC.Contributor" content="Shenghua Shi" /><meta name="DC.Contributor" content="Derek Stonich" /><meta name="DC.Contributor" content="Anton Cheltov" /><meta name="DC.Contributor" content="Ying Su" /><meta name="DC.Contributor" content="Arianna Mangravita-Novo" /><meta name="DC.Contributor" content="Michael Vicchiarelli" /><meta name="DC.Contributor" content="Danielle McAnally" /><meta name="DC.Contributor" content="Sylvia Kim" /><meta name="DC.Contributor" content="Hung Nguyen" /><meta name="DC.Contributor" content="Tina Kiffer Moreira" /><meta name="DC.Contributor" content="Layton H. Smith" /><meta name="DC.Contributor" content="Fu-Yue Zeng" /><meta name="DC.Contributor" content="Jena Diwan" /><meta name="DC.Contributor" content="Thomas D.Y. Chung" /><meta name="DC.Contributor" content="Anthony B. Pinkerton" /><meta name="DC.Contributor" content="Jonathan Kaunitz" /><meta name="DC.Contributor" content="José Luis Millán" /><meta name="DC.Date" content="2013/03/07" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK143562/" /><meta name="description" content="The isozymes of alkaline phosphatase (AP) are capable of dephosphorylation and transphosphorylation of a wide spectrum of substrates in vitro. Their localization in proximity to the cell surface suggests that they help facilitate the movement of substances across the plasma membrane. In humans, four isozymes of APs have been identified - one tissue-nonspecific (TNAP) and three tissue-specific isozymes named according to the tissue of their predominant expression: intestinal (IAP), placental (PLAP) and germ cell (GCAP) alkaline phosphatases." /><meta name="og:title" content="A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor" /><meta name="og:type" content="book" /><meta name="og:description" content="The isozymes of alkaline phosphatase (AP) are capable of dephosphorylation and transphosphorylation of a wide spectrum of substrates in vitro. Their localization in proximity to the cell surface suggests that they help facilitate the movement of substances across the plasma membrane. In humans, four isozymes of APs have been identified - one tissue-nonspecific (TNAP) and three tissue-specific isozymes named according to the tissue of their predominant expression: intestinal (IAP), placental (PLAP) and germ cell (GCAP) alkaline phosphatases." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK143562/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/mlprobe/ml260/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK143562/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><meta name="book-collection" content="NONE" />
|
||
|
||
<!-- Page meta end -->
|
||
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico" /><meta name="ncbi_phid" content="CE8E35337D660D510000000000AF0092.m_13" />
|
||
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3985586/3808861/4121862/3974050/3917732/251717/4216701/14534/45193/4113719/3849091/3984811/3751656/4033350/3840896/3577051/3852958/4008682/4207974/4206132/4062871/12930/3964959/3854974/36029/4128070/9685/3549676/3609192/3609193/3609213/3395586.css" /><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3411343/3882866.css" media="print" /></head>
|
||
<body class="book-part">
|
||
<div class="grid">
|
||
<div class="col twelve_col nomargin shadow">
|
||
<!-- System messages like service outage or JS required; this is handled by the TemplateResources portlet -->
|
||
<div class="sysmessages">
|
||
<noscript>
|
||
<p class="nojs">
|
||
<strong>Warning:</strong>
|
||
The NCBI web site requires JavaScript to function.
|
||
<a href="/guide/browsers/#enablejs" title="Learn how to enable JavaScript" target="_blank">more...</a>
|
||
</p>
|
||
</noscript>
|
||
</div>
|
||
<!--/.sysmessage-->
|
||
<div class="wrap">
|
||
<div class="page">
|
||
<div class="top">
|
||
<div id="universal_header">
|
||
<section class="usa-banner">
|
||
<div class="usa-accordion">
|
||
<header class="usa-banner-header">
|
||
<div class="usa-grid usa-banner-inner">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" />
|
||
<p>An official website of the United States government</p>
|
||
<button class="non-usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" type="button">
|
||
<span class="usa-banner-button-text">Here's how you know</span>
|
||
</button>
|
||
</div>
|
||
</header>
|
||
<div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" aria-hidden="true">
|
||
<div class="usa-banner-guidance-gov usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The .gov means it's official.</strong>
|
||
<br />
|
||
Federal government websites often end in .gov or .mil. Before
|
||
sharing sensitive information, make sure you're on a federal
|
||
government site.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
<div class="usa-banner-guidance-ssl usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The site is secure.</strong>
|
||
<br />
|
||
The <strong>https://</strong> ensures that you are connecting to the
|
||
official website and that any information you provide is encrypted
|
||
and transmitted securely.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<div class="usa-overlay"></div>
|
||
<header class="ncbi-header" role="banner" data-section="Header">
|
||
|
||
<div class="usa-grid">
|
||
<div class="usa-width-one-whole">
|
||
|
||
<div class="ncbi-header__logo">
|
||
<a href="/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" />
|
||
</a>
|
||
</div>
|
||
|
||
<div class="ncbi-header__account">
|
||
<a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a>
|
||
<button id="account_info" class="header-button" style="display:none" aria-controls="account_popup" type="button">
|
||
<span class="fa fa-user" aria-hidden="true">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" width="20px" height="20px">
|
||
<g style="fill: #fff">
|
||
<ellipse cx="12" cy="8" rx="5" ry="6"></ellipse>
|
||
<path d="M21.8,19.1c-0.9-1.8-2.6-3.3-4.8-4.2c-0.6-0.2-1.3-0.2-1.8,0.1c-1,0.6-2,0.9-3.2,0.9s-2.2-0.3-3.2-0.9 C8.3,14.8,7.6,14.7,7,15c-2.2,0.9-3.9,2.4-4.8,4.2C1.5,20.5,2.6,22,4.1,22h15.8C21.4,22,22.5,20.5,21.8,19.1z"></path>
|
||
</g>
|
||
</svg>
|
||
</span>
|
||
<span class="username desktop-only" aria-hidden="true" id="uname_short"></span>
|
||
<span class="sr-only">Show account info</span>
|
||
</button>
|
||
</div>
|
||
|
||
<div class="ncbi-popup-anchor">
|
||
<div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true">
|
||
<div class="ncbi-popup-head">
|
||
<button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu" type="button">
|
||
<span class="fa fa-times">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 48 48" width="24px" height="24px">
|
||
<path d="M38 12.83l-2.83-2.83-11.17 11.17-11.17-11.17-2.83 2.83 11.17 11.17-11.17 11.17 2.83 2.83 11.17-11.17 11.17 11.17 2.83-2.83-11.17-11.17z"></path>
|
||
</svg>
|
||
</span>
|
||
<span class="usa-sr-only">Close</span></button>
|
||
<h4>Account</h4>
|
||
</div>
|
||
<div class="account-user-info">
|
||
Logged in as:<br />
|
||
<b><span class="username" id="uname_long">username</span></b>
|
||
</div>
|
||
<div class="account-links">
|
||
<ul class="usa-unstyled-list">
|
||
<li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li>
|
||
<li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li>
|
||
<li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li>
|
||
<li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</header>
|
||
<div role="navigation" aria-label="access keys">
|
||
<a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a>
|
||
<a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a>
|
||
<a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a>
|
||
<a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a>
|
||
<a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a>
|
||
</div>
|
||
<section data-section="Alerts">
|
||
<div class="ncbi-alerts-placeholder"></div>
|
||
</section>
|
||
</div>
|
||
<div class="header">
|
||
<div class="res_logo"><h1 class="res_name"><a href="/books/" title="Bookshelf home">Bookshelf</a></h1><h2 class="res_tagline"></h2></div>
|
||
<div class="search"><form method="get" action="/books/"><div class="search_form"><label for="database" class="offscreen_noflow">Search database</label><select id="database"><optgroup label="Recent"><option value="books" selected="selected" data-ac_dict="bookshelf-search">Books</option><option value="pubmed">PubMed</option><option value="clinvar">ClinVar</option><option value="refseq" class="last">RefSeq</option></optgroup><optgroup label="All"><option value="gquery">All Databases</option><option value="assembly">Assembly</option><option value="biocollections">Biocollections</option><option value="bioproject">BioProject</option><option value="biosample">BioSample</option><option value="books" data-ac_dict="bookshelf-search">Books</option><option value="clinvar">ClinVar</option><option value="cdd">Conserved Domains</option><option value="gap">dbGaP</option><option value="dbvar">dbVar</option><option value="gene">Gene</option><option value="genome">Genome</option><option value="gds">GEO DataSets</option><option value="geoprofiles">GEO Profiles</option><option value="gtr">GTR</option><option value="ipg">Identical Protein Groups</option><option value="medgen">MedGen</option><option value="mesh">MeSH</option><option value="nlmcatalog">NLM Catalog</option><option value="nuccore">Nucleotide</option><option value="omim">OMIM</option><option value="pmc">PMC</option><option value="protein">Protein</option><option value="proteinclusters">Protein Clusters</option><option value="protfam">Protein Family Models</option><option value="pcassay">PubChem BioAssay</option><option value="pccompound">PubChem Compound</option><option value="pcsubstance">PubChem Substance</option><option value="pubmed">PubMed</option><option value="snp">SNP</option><option value="sra">SRA</option><option value="structure">Structure</option><option value="taxonomy">Taxonomy</option><option value="toolkit">ToolKit</option><option value="toolkitall">ToolKitAll</option><option value="toolkitbookgh">ToolKitBookgh</option></optgroup></select><div class="nowrap"><label for="term" class="offscreen_noflow" accesskey="/">Search term</label><div class="nowrap"><input type="text" name="term" id="term" title="Search Books. Use up and down arrows to choose an item from the autocomplete." value="" class="jig-ncbiclearbutton jig-ncbiautocomplete" data-jigconfig="dictionary:'bookshelf-search',disableUrl:'NcbiSearchBarAutoComplCtrl'" autocomplete="off" data-sbconfig="ds:'no',pjs:'no',afs:'no'" /></div><button id="search" type="submit" class="button_search nowrap" cmd="go">Search</button></div></div></form><ul class="searchlinks inline_list"><li>
|
||
<a href="/books/browse/">Browse Titles</a>
|
||
</li><li>
|
||
<a href="/books/advanced/">Advanced</a>
|
||
</li><li class="help">
|
||
<a href="/books/NBK3833/">Help</a>
|
||
</li><li class="disclaimer">
|
||
<a target="_blank" data-ga-category="literature_resources" data-ga-action="link_click" data-ga-label="disclaimer_link" href="https://www.ncbi.nlm.nih.gov/books/about/disclaimer/">Disclaimer</a>
|
||
</li></ul></div>
|
||
</div>
|
||
|
||
|
||
|
||
<!--<component id="Page" label="headcontent"/>-->
|
||
|
||
</div>
|
||
<div class="content">
|
||
<!-- site messages -->
|
||
<!-- Custom content 1 -->
|
||
<div class="col1">
|
||
|
||
</div>
|
||
|
||
<div class="container">
|
||
<div id="maincontent" class="content eight_col col">
|
||
<!-- Custom content in the left column above book nav -->
|
||
<div class="col2">
|
||
|
||
</div>
|
||
|
||
<!-- Book content -->
|
||
|
||
|
||
<!-- Custom content between navigation and content -->
|
||
<div class="col3">
|
||
|
||
</div>
|
||
|
||
<div class="document">
|
||
<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/mlprobe/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-mlprobe-lrg.png" alt="Cover of Probe Reports from the NIH Molecular Libraries Program" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>Probe Reports from the NIH Molecular Libraries Program [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK143562_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK143562_dtls__"><div>Bethesda (MD): National Center for Biotechnology Information (US); 2010-.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/mlprobe/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml262/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml258/" title="Next page in this title">Next ></a></div></div></div></div></div>
|
||
<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK143562_"><span class="title" itemprop="name">A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor</span></h1><p class="contrib-group"><span itemprop="author">Santhi Ganji</span>, <span itemprop="author">Jiwen Zou</span>, <span itemprop="author">Brock Brown</span>, <span itemprop="author">Ekaterina V. Bobkova</span>, <span itemprop="author">Robert Ardecky</span>, <span itemprop="author">Craig Rosenstein</span>, <span itemprop="author">Ian Pass</span>, <span itemprop="author">Russell Dahl</span>, <span itemprop="author">Stefan Vasile</span>, <span itemprop="author">Eduard Sergienko</span>, <span itemprop="author">Shenghua Shi</span>, <span itemprop="author">Derek Stonich</span>, <span itemprop="author">Anton Cheltov</span>, <span itemprop="author">Ying Su</span>, <span itemprop="author">Arianna Mangravita-Novo</span>, <span itemprop="author">Michael Vicchiarelli</span>, <span itemprop="author">Danielle McAnally</span>, <span itemprop="author">Sylvia Kim</span>, <span itemprop="author">Hung Nguyen</span>, <span itemprop="author">Tina Kiffer Moreira</span>, <span itemprop="author">Layton H. Smith</span>, <span itemprop="author">Fu-Yue Zeng</span>, <span itemprop="author">Jena Diwan</span>, <span itemprop="author">Thomas D.Y. Chung</span>, <span itemprop="author">Anthony B. Pinkerton</span>, <span itemprop="author">Jonathan Kaunitz</span>, and <span itemprop="author">José Luis Millán</span>.</p><a data-jig="ncbitoggler" href="#__NBK143562_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK143562_ai__"><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Santhi Ganji</span>,<sup>1</sup> <span itemprop="author">Jiwen Zou</span>,<sup>1</sup> <span itemprop="author">Brock Brown</span>,<sup>1</sup> <span itemprop="author">Ekaterina V. Bobkova</span>,<sup>1</sup> <span itemprop="author">Robert Ardecky</span>,<sup>1</sup> <span itemprop="author">Craig Rosenstein</span>,<sup>2</sup> <span itemprop="author">Ian Pass</span>,<sup>1</sup> <span itemprop="author">Russell Dahl</span>,<sup>1</sup> <span itemprop="author">Stefan Vasile</span>,<sup>2</sup> <span itemprop="author">Eduard Sergienko</span>,<sup>1</sup> <span itemprop="author">Shenghua Shi</span>,<sup>1</sup> <span itemprop="author">Derek Stonich</span>,<sup>1</sup> <span itemprop="author">Anton Cheltov</span>,<sup>1</sup> <span itemprop="author">Ying Su</span>,<sup>1</sup> <span itemprop="author">Arianna Mangravita-Novo</span>,<sup>2</sup> <span itemprop="author">Michael Vicchiarelli</span>,<sup>2</sup> <span itemprop="author">Danielle McAnally</span>,<sup>2</sup> <span itemprop="author">Sylvia Kim</span>,<sup>1</sup> <span itemprop="author">Hung Nguyen</span>,<sup>1</sup> <span itemprop="author">Tina Kiffer Moreira</span>,<sup>3</sup> <span itemprop="author">Layton H. Smith</span>,<sup>2</sup> <span itemprop="author">Fu-Yue Zeng</span>,<sup>1</sup> <span itemprop="author">Jena Diwan</span>,<sup>1</sup> <span itemprop="author">Thomas D.Y. Chung</span>,<sup>1</sup> <span itemprop="author">Anthony B. Pinkerton</span>,<sup>1</sup> <span itemprop="author">Jonathan Kaunitz</span>,<sup>4</sup> and <span itemprop="author">José Luis Millán</span><sup>3</sup>.<sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup></p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup>
|
||
Sanford-Burnham Center for Chemical Genomics at Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.</div><div class="affiliation"><sup>2</sup>
|
||
Sanford-Burnham Center for Chemical Genomics at Sanford-Burnham Medical Research Institute, Orlando, Florida 32827, USA.</div><div class="affiliation"><sup>3</sup>
|
||
Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.</div><div class="affiliation"><sup>4</sup>
|
||
University of California, Los Angeles, School of Medicine, Veterans Hospital, Los Angeles, CA 90073</div><div class="affiliation"><sup><img src="/corehtml/pmc/pmcgifs/corrauth.gif" alt="corresponding author" /></sup>Corresponding author: Anthony B. Pinkerton, Ph.D.
|
||
<span class="before-email-separator"></span><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.mahnrubdrofnas@notreknipa" class="oemail">gro.mahnrubdrofnas@notreknipa</a></div></div><p class="small">Received: <span itemprop="datePublished">October 31, 2011</span>; Last Update: <span itemprop="dateModified">March 7, 2013</span>.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p>The isozymes of alkaline phosphatase (AP) are capable of dephosphorylation and transphosphorylation of a wide spectrum of substrates <i>in vitro</i>. Their localization in proximity to the cell surface suggests that they help facilitate the movement of substances across the plasma membrane. In humans, four isozymes of APs have been identified - one tissue-nonspecific (TNAP) and three tissue-specific isozymes named according to the tissue of their predominant expression: intestinal (IAP), placental (PLAP) and germ cell (GCAP) alkaline phosphatases.</p><p>This project sought to identify isozyme and species selective inhibitors and activators of the human and mouse alkaline phosphatases. Concurrent high throughput screening (HTS) campaigns of the NIH Molecular Libraries Small Molecule Repository (MLSMR) library comprising ~355,000 compounds were completed against murine IAP (muIAP), human IAP (huIAP), TNAP and PLAP (<i>TNAP & PLAP are only found in humans</i>) were completed. This Center Probe Report describes the screens and structure activity relationship (SAR) elucidation that led to identification of a potent (540 nM IC<sub>50</sub>) inhibitor of the murine IAP (muIAP), with 65-fold selectivity against TNAP and >185-fold selectivity against PLAP as well as the human isoform of IAP (huIAP).</p></div><div class="h2"></div><p><b>Assigned Assay Grant #:</b> X01-MH077602-01</p><p><b>Screening Center Name & PI:</b> Sanford-Burnham Medical Research Institute & John C. Reed, M.D., Ph.D.</p><p><b>Chemistry Center Name & PI:</b> Sanford-Burnham Medical Research Institute & John C. Reed, M.D., Ph.D.</p><p><b>Assay Submitter & Institution:</b> Sanford-Burnham Medical Research Institute & José Luis Millán (PI)</p><p>University of California, Los Angeles, School of Medicine & Jonathan Kaunitz (co-PI)</p><p><b>PubChem Summary Bioassay Identifier (AID):</b>
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/bioassay/2818" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">2818</a></p><div id="ml260.s1"><h2 id="_ml260_s1_">Probe Structure & Characteristics</h2><p>This Center Probe Report describes a selective and murine species-specific intestinal alkaline phosphatase (muIAP) inhibitor probe <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a>. Potency and selectivity characteristics are summarized for this probe in <a class="figpopup" href="/books/NBK143562/table/ml260.t1/?report=objectonly" target="object" rid-figpopup="figml260t1" rid-ob="figobml260t1">Table 1</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml260t1"><a href="/books/NBK143562/table/ml260.t1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figml260t1" rid-ob="figobml260t1"><img class="small-thumb" src="/books/NBK143562/table/ml260.t1/?report=thumb" src-large="/books/NBK143562/table/ml260.t1/?report=previmg" alt="Table 1. Biological activity summary & AIDs for Probes." /></a><div class="icnblk_cntnt"><h4 id="ml260.t1"><a href="/books/NBK143562/table/ml260.t1/?report=objectonly" target="object" rid-ob="figobml260t1">Table 1</a></h4><p class="float-caption no_bottom_margin">Biological activity summary & AIDs for Probes. </p></div></div><div id="ml260.fu1" class="figure"><div class="graphic"><img src="/books/NBK143562/bin/ml260fu1.jpg" alt="Image ml260fu1" /></div></div></div><div id="ml260.s2"><h2 id="_ml260_s2_">1. Recommendations for Scientific Use of the Probe</h2><p>To the present date, the scientific research community has no good selective inhibitors of mouse intestinal alkaline phosphatase (muIAP) that discriminate between the activity of the tissue-specific isozymes of AP, murine, or human in origin, such as the mouse embryonic AP, product of the Akp5 gene and global intestinal AP, product of the Akp6 locus, or the human Placental AP (PLAP) and germ cell AP (GCAP)), to assist in elucidating its functional and physiological roles. Such roles include detoxifying bacterial endotoxins and thereby acting in the establishment of gut mucosal tolerance towards the microbiota, functioning as a rate-determining step in the absorption of fatty acids, and in the regulation of duodenal surface pH and ATP concentration. This probe can be applied to the analysis of physiologic role of IAPs and other isozymes in the gut in mouse models and in the examination of the many other hydrolytic enzymes relating to ATP release mechanisms, which are otherwise obscured by the rapid hydrolysis of ATP at the cell surface. In fact, given that the mouse <i>Akp3</i> (muIAP), <i>Akp5,</i> and <i>Akp6</i> genes are syntenic and very close together in the chromosome, obtaining double knock-out (KO) mice (e.g. <i>Akp3/Akp6</i> double KO, or <i>Akp3/Akp5</i> double KOs) to investigate function is next to impossible. So, the ability to inhibit <i>Akp3</i> (muIAP) through a chemical probe in an Akp5 or Akp6 KO mouse models will help us dissect the distinct functions of these isozymes.</p><p>The somewhat unexpected species selectivity of <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> indeed provides a tool to elucidate the molecular interactions and structural determinants of selective inhibition in the purified enzymes.</p><p>It can also be applied to the study of the basic biology of plasma membrane fatty acid uptake and the biology of pulmonary inflammation induced by pathogens. It is hoped that scientists interested in the basic biology of human AP and those interested in translational applications of that research, such as gastrointestinal and pulmonary physiologists with interests in obesity, intestinal lipid uptake, and cystic fibrosis, will find this probe of interest.</p></div><div id="ml260.s3"><h2 id="_ml260_s3_">2. Materials and Methods</h2><div id="ml260.s4"><h3>2.1. Assays</h3><p><a class="figpopup" href="/books/NBK143562/table/ml260.t2/?report=objectonly" target="object" rid-figpopup="figml260t2" rid-ob="figobml260t2">Table 2</a> summarizes the details for the assays that drove this probe project and can be found in the “Assay Description” section under the listed AIDs in <a class="figpopup" href="/books/NBK143562/table/ml260.t2/?report=objectonly" target="object" rid-figpopup="figml260t2" rid-ob="figobml260t2">Table 2</a> as viewable in <a href="/pcassay" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PubChem Bioassays</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml260t2"><a href="/books/NBK143562/table/ml260.t2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figml260t2" rid-ob="figobml260t2"><img class="small-thumb" src="/books/NBK143562/table/ml260.t2/?report=thumb" src-large="/books/NBK143562/table/ml260.t2/?report=previmg" alt="Table 2. Summary of Assays and AIDs." /></a><div class="icnblk_cntnt"><h4 id="ml260.t2"><a href="/books/NBK143562/table/ml260.t2/?report=objectonly" target="object" rid-ob="figobml260t2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of Assays and AIDs. </p></div></div></div><div id="ml260.s5"><h3>2.2. Probe Chemical Characterization</h3><div id="ml260.s6"><h4>Chemical name of probe compound & structure including stereochemistry</h4><p>The IUPAC name of the probe is <i>N</i>-(2,5-dimethylphenyl)-2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetamide. The actual batch prepared, tested, and submitted to the MLSMR is archived as <a href="https://pubchem.ncbi.nlm.nih.gov/substance/124756790" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 124756790</a> corresponding to CID 50919367. It has no chiral centers. The probe molecule is not commercially available. A 20 mg sample of <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> synthesized at SBCCG has been deposited in the MLSMR (Bio-Focus DPI) (see Probe Submission <a class="figpopup" href="/books/NBK143562/table/ml260.t3/?report=objectonly" target="object" rid-figpopup="figml260t3" rid-ob="figobml260t3">Table 3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml260t3"><a href="/books/NBK143562/table/ml260.t3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figml260t3" rid-ob="figobml260t3"><img class="small-thumb" src="/books/NBK143562/table/ml260.t3/?report=thumb" src-large="/books/NBK143562/table/ml260.t3/?report=previmg" alt="Table 3. Probe and Analog Submissions to MLSMR (BioFocus DPI) for muIAP Inhibitors." /></a><div class="icnblk_cntnt"><h4 id="ml260.t3"><a href="/books/NBK143562/table/ml260.t3/?report=objectonly" target="object" rid-ob="figobml260t3">Table 3</a></h4><p class="float-caption no_bottom_margin">Probe and Analog Submissions to MLSMR (BioFocus DPI) for muIAP Inhibitors. </p></div></div><div id="ml260.f1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK143562/bin/ml260f1.jpg" alt="Figure 1. Structure of ML260." /></div><h3><span class="label">Figure 1</span><span class="title">Structure of ML260</span></h3></div><p><b>Synthetic Scheme and Structural Verification</b>. Probe <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a>
|
||
<a href="https://pubchem.ncbi.nlm.nih.gov/substance/124756790" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">SID 124756790</a> corresponding to CID 50919367 was synthesized according to <a class="figpopup" href="/books/NBK143562/figure/ml260.f8/?report=objectonly" target="object" rid-figpopup="figml260f8" rid-ob="figobml260f8">Scheme 1</a>, and <a class="figpopup" href="/books/NBK143562/figure/ml260.f2/?report=objectonly" target="object" rid-figpopup="figml260f2" rid-ob="figobml260f2">Figs. 2</a> and <a class="figpopup" href="/books/NBK143562/figure/ml260.f3/?report=objectonly" target="object" rid-figpopup="figml260f3" rid-ob="figobml260f3">3</a> provide <sup>1</sup>H NMR and LC-MS structure proof, respectively.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f8" co-legend-rid="figlgndml260f8"><a href="/books/NBK143562/figure/ml260.f8/?report=objectonly" target="object" title="Scheme 1" class="img_link icnblk_img figpopup" rid-figpopup="figml260f8" rid-ob="figobml260f8"><img class="small-thumb" src="/books/NBK143562/bin/ml260f8.gif" src-large="/books/NBK143562/bin/ml260f8.jpg" alt="Scheme 1. Synthesis of ML260." /></a><div class="icnblk_cntnt" id="figlgndml260f8"><h4 id="ml260.f8"><a href="/books/NBK143562/figure/ml260.f8/?report=objectonly" target="object" rid-ob="figobml260f8">Scheme 1</a></h4><p class="float-caption no_bottom_margin">Synthesis of ML260. conditions: <i>a</i>. dichloromethane, triethylamine, (88% yield); <i>b</i>. trifluoroacetic acid, dichloromethane, 0°C warm to RT (100% yield); <i>c</i>. EDC, HOBT, NMM, DMF, (55%) </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f2" co-legend-rid="figlgndml260f2"><a href="/books/NBK143562/figure/ml260.f2/?report=objectonly" target="object" title="Figure 2" class="img_link icnblk_img figpopup" rid-figpopup="figml260f2" rid-ob="figobml260f2"><img class="small-thumb" src="/books/NBK143562/bin/ml260f2.gif" src-large="/books/NBK143562/bin/ml260f2.jpg" alt="Figure 2. 1H NMR Spectrum of ML260." /></a><div class="icnblk_cntnt" id="figlgndml260f2"><h4 id="ml260.f2"><a href="/books/NBK143562/figure/ml260.f2/?report=objectonly" target="object" rid-ob="figobml260f2">Figure 2</a></h4><p class="float-caption no_bottom_margin"><sup>1</sup>H NMR Spectrum of ML260. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f3" co-legend-rid="figlgndml260f3"><a href="/books/NBK143562/figure/ml260.f3/?report=objectonly" target="object" title="Figure 3" class="img_link icnblk_img figpopup" rid-figpopup="figml260f3" rid-ob="figobml260f3"><img class="small-thumb" src="/books/NBK143562/bin/ml260f3.gif" src-large="/books/NBK143562/bin/ml260f3.jpg" alt="Figure 3. LC-MS for ML260." /></a><div class="icnblk_cntnt" id="figlgndml260f3"><h4 id="ml260.f3"><a href="/books/NBK143562/figure/ml260.f3/?report=objectonly" target="object" rid-ob="figobml260f3">Figure 3</a></h4><p class="float-caption no_bottom_margin">LC-MS for ML260. (Reverse phase C18 column: isocratic) </p></div></div></div><div id="ml260.s7"><h4>Solubility and Stability of probe in PBS at room temperature</h4><p>The stability and solubility of <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> was investigated in phosphate-buffered saline (PBS) at room temperature (<a class="figpopup" href="/books/NBK143562/figure/ml260.f4/?report=objectonly" target="object" rid-figpopup="figml260f4" rid-ob="figobml260f4">Figure 4</a>). A comparison of the %parent compound remaining at various times indicates that the compound is very stable for much more than 48 hrs.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f4" co-legend-rid="figlgndml260f4"><a href="/books/NBK143562/figure/ml260.f4/?report=objectonly" target="object" title="Figure 4" class="img_link icnblk_img figpopup" rid-figpopup="figml260f4" rid-ob="figobml260f4"><img class="small-thumb" src="/books/NBK143562/bin/ml260f4.gif" src-large="/books/NBK143562/bin/ml260f4.jpg" alt="Figure 4. Stability of ML260 in 1:1 acetonitrile:PBS at room temperature." /></a><div class="icnblk_cntnt" id="figlgndml260f4"><h4 id="ml260.f4"><a href="/books/NBK143562/figure/ml260.f4/?report=objectonly" target="object" rid-ob="figobml260f4">Figure 4</a></h4><p class="float-caption no_bottom_margin">Stability of ML260 in 1:1 acetonitrile:PBS at room temperature. </p></div></div></div><div id="ml260.s8"><h4>MLS# that were submitted to the SMR collection</h4><p>Samples of the probe and five analogs synthesized at SBCCG were submitted to MLSMR (<a class="figpopup" href="/books/NBK143562/table/ml260.t3/?report=objectonly" target="object" rid-figpopup="figml260t3" rid-ob="figobml260t3">Table 3</a>).</p></div></div><div id="ml260.s9"><h3>2.3. Probe Preparation</h3><p>(compound numbering according to <a class="figpopup" href="/books/NBK143562/figure/ml260.f8/?report=objectonly" target="object" rid-figpopup="figml260f8" rid-ob="figobml260f8">Scheme 1</a>)</p><div id="ml260.s10"><h4>Preparation of tert-butyl 2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetate</h4><div id="ml260.fu2" class="figure"><div class="graphic"><img src="/books/NBK143562/bin/ml260fu2.jpg" alt="Image ml260fu2" /></div></div><p>2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonyl chloride <b>1</b> (2.33 g, 0.01 mol) was dissolved in 50 mL of methylene chloride containing 1 mL of triethylamine. The solution was cooled to 0°C in an ice bath and a solution of tert-butyl 2-aminoacetate (1.31 g, 0.01 mol) in 20 mL of methylene chloride was slowly added. The reaction was warmed to room temperature and when the reaction was determined to be complete by TLC, approximately 1-hour, the reaction mixture was poured into 100 mL of water, washed successively 100 mL of saturated sodium bicarbonate, 100 mL of brine, and the resultant organic phase was then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was chromatographed on silica gel and eluted with methylene chloride to yield 2.90 g of compound <b>2</b> (88 % yield), MS ESI <i>m/z</i> 329 [M+H].</p></div><div id="ml260.s11"><h4>Preparation of 2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetic acid</h4><div id="ml260.fu3" class="figure"><div class="graphic"><img src="/books/NBK143562/bin/ml260fu3.jpg" alt="Image ml260fu3" /></div></div><p>Tert-butyl 2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetate <b>2</b> (2.90g, 8.8 mmol) was dissolved in 100 mL of methylene chloride and the solution was cooled to 0°C in an ice bath. At his point 10 mL of trifluoracetic acid was added and the reaction was allowed to warm to room temperature. When the reaction was determined to be complete by TLC, approximately 2-hours, the solvent was removed under reduced pressure. At this point, 50 mL of toluene and 50 mL of methylene chloride was added to the crude reaction mixture and the solvent was removed under reduced pressure. This procedure was repeated two more times and the flask was put under high vacuum for 30 minutes. The grey solid 2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetic acid <b>3</b> (2.4 g, 100 %) was not purified further and was used as isolated in the next step. MS ESI <i>m/z</i> 273 [M+H].</p></div><div id="ml260.s12"><h4>Preparation of <i>N</i>-(2,5-dimethylphenyl)-2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido) acet-amide</h4><div id="ml260.fu4" class="figure"><div class="graphic"><img src="/books/NBK143562/bin/ml260fu4.jpg" alt="Image ml260fu4" /></div></div><p>2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetic acid <b>3</b> (0.27 g, 1 mmol) was dissolved in 3 mL of dimethylformamide and EDC (0.21g, 1.1 mol), HOBT (0.17g, 1.1 mmol) and 0.5 mL of NMM was added to the solution. The reaction mixture was stirred for 30 minutes at room temperature and then a solution of 2,5-dimethylaniline <b>4</b> (0.24g 2 mmol) in 1 mL of dimethylformamide was added. The reaction was stirred overnight at room temperature and then the solvent was removed under reduced pressure. The residue was dissolved in 30 mL of ethyl acetate and the organic layer was poured into 100 mL of water, washed successively 50 mL of saturated sodium bicarbonate, 50 mL of 1 N HCl, 50 mL of brine, and the resultant organic phase was then dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was chromatographed on silica gel and eluted with methylene chloride: ethyl acetate using a gradient of 100:1 to 90:10, to yield N-(2,5-dimethylphenyl)-2-(2-oxo-2,3-dihydrobenzo[d]oxazole-6-sulfonamido)acetamide <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> (0.20 g, 55 % yield), <sup>1</sup>H NMR (400 MHz, CDCl<sub>3</sub>) δ 9.18 (s, 1H), 8.08 (b, 1H), 7.71 (s, 1H), 7.67 (d, J = 6.7 Hz, 1H), 7.24 (d, J = 6.7 Hz, 1 H), 7.05 (d, J = 6.7 Hz, 1H), 6.98 (S, 1H), 6.84 (d, J = 6.7 Hz, 1H),3.66 (s, 2H), 2.49 (s, 3H), 2.19 (s, 3H), MS ESI <i>m/z</i> 376 [M+H].</p></div></div></div><div id="ml260.s13"><h2 id="_ml260_s13_">3. Results</h2><div id="ml260.s14"><h3>3.1. Dose Response Curves for Probe</h3><p>The multiple dose response titrations in <a class="figpopup" href="/books/NBK143562/figure/ml260.f5/?report=objectonly" target="object" rid-figpopup="figml260f5" rid-ob="figobml260f5">Figure 5</a> (on the right) of the probe <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> against muIAP, TNAP and PLAP highlight the 65-fold selectivity of it against TNAP and the more than 185-fold selectivity against PLAP.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f5" co-legend-rid="figlgndml260f5"><a href="/books/NBK143562/figure/ml260.f5/?report=objectonly" target="object" title="Figure 5" class="img_link icnblk_img figpopup" rid-figpopup="figml260f5" rid-ob="figobml260f5"><img class="small-thumb" src="/books/NBK143562/bin/ml260f5.gif" src-large="/books/NBK143562/bin/ml260f5.jpg" alt="Figure 5. Multiple dose response titrations of ML260." /></a><div class="icnblk_cntnt" id="figlgndml260f5"><h4 id="ml260.f5"><a href="/books/NBK143562/figure/ml260.f5/?report=objectonly" target="object" rid-ob="figobml260f5">Figure 5</a></h4><p class="float-caption no_bottom_margin">Multiple dose response titrations of ML260. </p></div></div></div><div id="ml260.s15"><h3>3.2. Cellular Activity</h3><p>This probe is an <i>in vitro</i> inhibitor, the assay providers’ (PI and co-PI) respective laboratories will conduct further profiling and will determine the translation of these activities in further <i>in vitro</i> then <i>in vivo</i> models.</p></div><div id="ml260.s16"><h3>3.3. Profiling Assays</h3><p>The probe was evaluated in a detailed <i>in vitro</i> pharmacology panel as shown in <a class="figpopup" href="/books/NBK143562/table/ml260.t4/?report=objectonly" target="object" rid-figpopup="figml260t4" rid-ob="figobml260t4">Table 4</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figml260t4"><a href="/books/NBK143562/table/ml260.t4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figml260t4" rid-ob="figobml260t4"><img class="small-thumb" src="/books/NBK143562/table/ml260.t4/?report=thumb" src-large="/books/NBK143562/table/ml260.t4/?report=previmg" alt="Table 4. Summary of in vitro ADME Properties of Novel Selection of muIAP Inhibitor Probe ML260." /></a><div class="icnblk_cntnt"><h4 id="ml260.t4"><a href="/books/NBK143562/table/ml260.t4/?report=objectonly" target="object" rid-ob="figobml260t4">Table 4</a></h4><p class="float-caption no_bottom_margin">Summary of <i>in vitro</i> ADME Properties of Novel Selection of muIAP Inhibitor Probe ML260. </p></div></div><p><a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> is very soluble in aqueous media at pH 5.0/6.2/7.4 at more than 400-fold higher concentration than the potency of the probe for muIAP (IC<sub>50</sub> = 540 nM) at all pH’s tested.</p><p>The PAMPA (<b>P</b>arallel <b>A</b>rtificial <b>M</b>embrane <b>P</b>ermeability <b>A</b>ssay) assay is used as an <i>in vitro</i> model of passive, transcellular permeability. An artificial membrane immobilized on a filter is placed between a donor and acceptor compartment. At the start of the test, drug is introduced in the donor compartment. Following the permeation period, the concentration of drug in the donor and acceptor compartments is measured using UV spectroscopy. Consistent with the predicted LogP, <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> is moderately permeable in this assay.</p><p>Plasma Protein Binding is a measure of a drug’s efficiency to bind to the proteins within blood plasma. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. Highly plasma protein bound drugs are confined to the vascular space, thereby having a relatively low volume of distribution. In contrast, drugs that remain largely unbound in plasma are generally available for distribution to other organs and tissues. <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> shows high binding to plasma proteins in human plasma at 1 μM and at 10 μM concentration. We were unable to determine a value for protein binding in mouse plasma, since the apparent amount of <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> in the plasma chamber was lower than in the reference chamber, which is consistent with its lower stability in mouse plasma.</p><p>Plasma Stability is a measure of the stability of small molecules and peptides in plasma and is an important parameter, which strongly can influence the <i>in vivo</i> efficacy of a test compound. Drug candidates are exposed in plasma to enzymatic processes (proteinases, esterases), and they can undergo intramolecular rearrangement or bind irreversibly (covalently) to proteins. <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> shows excellent stability in human and poor stability in mouse plasma. Mouse plasma is known to contain higher levels of these enzymes and additional enzymes, which may account for this poor stability.</p><p>The microsomal stability assay is commonly used to rank compounds according to their metabolic stability. This assay addresses the pharmacologic question of how long the parent compound will remain circulating in plasma within the body. <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> shows relatively poor stability in human liver homogenates, and good stability in mouse liver homogenates that may improve the utility of this probe in <i>in vivo</i> rodent models with respect to hepatic metabolism, though this may be confounded with its apparently poor plasma stability in mice.</p></div></div><div id="ml260.s17"><h2 id="_ml260_s17_">4. Discussion</h2><p>The isozymes of alkaline phosphatase (AP; orthophosphoric monoester phosphohydrolase, EC 3.1.3.1)
|
||
are ectoenzymes anchored onto the cytoplasmic membrane via a phosphatidylinositol glycan moiety<sup><a class="bk_pop" href="#ml260.r1">1</a>,<a class="bk_pop" href="#ml260.r2">2</a></sup>. They are
|
||
capable of catalyzing dephosphorylation and transphosphorylation reactions of a wide spectrum of
|
||
substrates <i>in vitro</i><a class="bk_pop" href="#ml260.r2">2</a>. These selective
|
||
probe(s) will be useful in elucidating the functional roles of human and mouse IAPs in 1)
|
||
detoxifying bacterial endotoxins and thereby acting in the establishment of gut mucosal tolerance towards the microbiota<sup><a class="bk_pop" href="#ml260.r3">3</a></sup>; 2) their function as a rate-limiting step in the absorption of fatty acids<sup><a class="bk_pop" href="#ml260.r4">4</a>–<a class="bk_pop" href="#ml260.r6">6</a></sup>; and 3) in its role in influencing bicarbonate secretion in the gut<sub><a class="bk_pop" href="#ml260.r7">7</a></sub>. In addition, high potency selective inhibitors of IAP isozymes would facilitate studies of ecto-purinergic regulation of duodenal bicarbonate secretion, examining the many ATP phosphohydrolases present in the intestinal brush border, which would enable the study of ATP release mechanisms<sup><a class="bk_pop" href="#ml260.r8">8</a></sup>. With respect to these latter three biological questions the role of IAP in gut biology, the most relevant selectivities towards potential “off-target” activities are for the highly expressed (and readily available) isozymes, TNAP and PLAP, As most initial studies would be in mice, we chose to drive probe development through the potency against muIAP and selectivity against huIAP, TNAP and PLAP as shown in <a class="figpopup" href="/books/NBK143562/table/ml260.t1/?report=objectonly" target="object" rid-figpopup="figml260t1" rid-ob="figobml260t1">Table 1</a>.</p><div id="ml260.s18"><h3>4.1. Comparison to Existing Art and How the New Probe is an Improvement</h3><p>During the Molecular Library Screening Center Network (MLSCN) pilot phase or the Molecular
|
||
Libraries Initiative (MLI), we developed a triazole probe <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a> (CID 294673, <a class="figpopup" href="/books/NBK143562/figure/ml260.f6/?report=objectonly" target="object" rid-figpopup="figml260f6" rid-ob="figobml260f6">Figure 6</a>) (<i><a href="https://mli.nih.gov/mli/?dl_id=712" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://mli.nih.gov/mli/?dl_id=712</a></i>) that was more selective for the human IAP instead of TNAP (795 nM IC<sub>50</sub>; 6.5-fold) or PLAP (4,810 nM IC<sub>50</sub>; 39-fold) and exhibited a novel mode of action: uncompetitive versus the phosphate-donor substrate. While this probe is the most potent human IAP inhibitor (122 nM in the huIAP luminescent assay) known thus far, it represents <i><u>only one</u></i> scaffold and the <i><u>species specificity</u></i> was not examined.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f6" co-legend-rid="figlgndml260f6"><a href="/books/NBK143562/figure/ml260.f6/?report=objectonly" target="object" title="Figure 6" class="img_link icnblk_img figpopup" rid-figpopup="figml260f6" rid-ob="figobml260f6"><img class="small-thumb" src="/books/NBK143562/bin/ml260f6.gif" src-large="/books/NBK143562/bin/ml260f6.jpg" alt="Figure 6. ML038 (CID 2946732)." /></a><div class="icnblk_cntnt" id="figlgndml260f6"><h4 id="ml260.f6"><a href="/books/NBK143562/figure/ml260.f6/?report=objectonly" target="object" rid-ob="figobml260f6">Figure 6</a></h4><p class="float-caption no_bottom_margin">ML038 (CID 2946732). </p></div></div><p>From a recent survey of the literature and SciFinder patent search, there are very few examples of intestinal alkaline phosphatase (IAP) inhibitors (and no activators) that show selectivity for the target over the other alkaline phosphatase isozymes (PLAP, TNAP) in the literature. A recent disclosure of modulators, i.e., activators and inhibitors, of Intestinal Alkaline Phosphatase (IAP) describes classes of molecules that can be used for treating bacterial infections of the intestinal tract and methods for maintaining the health of the intestinal tract using IAP activators. However, no selectivity data is presented for these compounds. Further disclosed are methods to assist in weight gain of emaciated patients and those having reduced or negligible fat absorption using IAP inhibitors (US2010/0016313 A1). A representative molecule from this patent is illustrated in <a class="figpopup" href="/books/NBK143562/figure/ml260.f7/?report=objectonly" target="object" rid-figpopup="figml260f7" rid-ob="figobml260f7">Figure 7</a>.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figml260f7" co-legend-rid="figlgndml260f7"><a href="/books/NBK143562/figure/ml260.f7/?report=objectonly" target="object" title="Figure 7" class="img_link icnblk_img figpopup" rid-figpopup="figml260f7" rid-ob="figobml260f7"><img class="small-thumb" src="/books/NBK143562/bin/ml260f7.gif" src-large="/books/NBK143562/bin/ml260f7.jpg" alt="Figure 7. Representative molecule from patent US2010/0016313 A1." /></a><div class="icnblk_cntnt" id="figlgndml260f7"><h4 id="ml260.f7"><a href="/books/NBK143562/figure/ml260.f7/?report=objectonly" target="object" rid-ob="figobml260f7">Figure 7</a></h4><p class="float-caption no_bottom_margin">Representative molecule from patent US2010/0016313 A1. </p></div></div><p>The probe described in this report represents a novel, chemically distinct, first-in-class inhibitor probe <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> of the mouse IAP isozyme, that is the most potent, sub-micromolar (muIAP IC<sub>50</sub> = 540 nM), and selective inhibitor reported for the enzyme from this species. As a comparison, its potency (muIAP IC<sub>50</sub> = 540 nM) for the mouse IAP, is comparable to that of the previous MLSCN probe <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a> (huIAP IC<sub>50</sub> = 122 nM) for the human enzyme, however it represents significant improvements in selectivity against the other isozymes, TNAP (65-fold <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> vs. 6.5-fold <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a>) and PLAP (>185-fold <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> vs. 39-fold <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a>). However, it should be noted that this probe is highly selective for the mouse <i>vs.</i> the human isoform. Our lab (Dr. Millán) has shown that the phylogenetic analysis shows that the mouse isozymes are closer in homology to each other than to the human isozymes [5], so our finding of such a species selective probe for muIAP validates this on an enzyme functional level. Also, the dihydrobenzo[d]oxazole-6-sulfonamido-acetamide core of <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> represents a completely different chemical scaffold as compared to the triazole scaffold of <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a>, so it will potentially offer a pharmacophore with different ADME/T PK properties than <a href="/pcsubstance/?term=ML038[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML038</a>. Indeed <a href="/pcsubstance/?term=ML260[synonym]" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=pubchem">ML260</a> has excellent solubility and stability properties.</p></div></div><div id="ml260.s19"><h2 id="_ml260_s19_">5. References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="ml260.r1">Low MG, Prasad AR. A phospholipase D specific for the phosphatidylinositol anchor of cell-surface proteins is abundant in plasma. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>1988;<span class="ref-vol">85</span>:980–984.</span> [<a href="/pmc/articles/PMC279684/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC279684</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/3422494" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3422494</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="ml260.r2">Millan JL. Alkaline Phosphatases: Structure, substrate specificity and functional relatedness to other members of a large super family of enzymes. <span><span class="ref-journal">In Purinergic Signalling. </span>2006;<span class="ref-vol">2</span>(2):335–341.</span> [Review] [<a href="/pmc/articles/PMC2254479/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2254479</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18404473" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18404473</span></a>]</div></dd><dt>3.</dt><dd><div class="bk_ref" id="ml260.r3">Goldberg RF, Austen WG Jr, Zhang X, Munene G, Mostafa G, Biswas S, McCormack M, Eberlin K, Nguyen JT, Tatlidede HS, Warren HS, Malo MS, Narisawa S, Millán JL, Hodin RA. Intestinal alkaline phosphatase is a gut defense factor maintained by enteral nutrition. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>2008;<span class="ref-vol">105</span>:3551–3556.</span> [<a href="/pmc/articles/PMC2265168/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2265168</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18292227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18292227</span></a>]</div></dd><dt>4.</dt><dd><div class="bk_ref" id="ml260.r4">Narisawa S, Huang L, Iwasaki A, Hasegawa H, Alpers DH, Millán JL. Accelerated fat absorption in intestinal alkaline phosphatase knockout mice. <span><span class="ref-journal">Mol Cell Biol. </span>2003;<span class="ref-vol">23</span>:7525–7530.</span> [<a href="/pmc/articles/PMC207564/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC207564</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14560000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14560000</span></a>]</div></dd><dt>5.</dt><dd><div class="bk_ref" id="ml260.r5">Narisawa S, Hoylaerts MF, Doctor KS, Fukuda MN, Alpers DH, Millán JL. A novel phosphatase upregulated in Akp3 knockout mice. <span><span class="ref-journal">Am J Physiol Gastrointest Liver Physiol. </span>2007;<span class="ref-vol">293</span>:1068–77.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17901166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17901166</span></a>]</div></dd><dt>6.</dt><dd><div class="bk_ref" id="ml260.r6">Nakano T, Inoue I, Koyama I, Kanazawa K, Nakamura K, Narisawa S, Tanaka K, Akita M, Masuyama T, Seo M, Hokari S, Katayama S, Alpers DH, Millán JL, Komoda T. Disruption of the murine intestinal alkaline phosphatase gene (Akp3) impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis. <span><span class="ref-journal">Am J Physiol Gastrointest Liver Physiol. </span>2007;<span class="ref-vol">292</span>:1439–1449.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17332477" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17332477</span></a>]</div></dd><dt>7.</dt><dd><div class="bk_ref" id="ml260.r7">Akiba Y, Watanabe C, Mizumori M, Kaunitz JD. Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. <span><span class="ref-journal">Am J Physiol Gastrointest Liver Physiol. </span>2009;<span class="ref-vol">297</span>(4):G781–791.</span> [<a href="/pmc/articles/PMC2763813/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2763813</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19643955" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19643955</span></a>]</div></dd><dt>8.</dt><dd><div class="bk_ref" id="ml260.r8">Mizumori M, Ham M, Guth PH, Engel E, Kaunitz JD, Akiba Y. Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum. <span><span class="ref-journal">J Physiol. </span>2009;<span class="ref-vol">587</span>(Pt 14):3651–63.</span> Epub 2009 May 18. [<a href="/pmc/articles/PMC2742288/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2742288</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19451200" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19451200</span></a>]</div></dd></dl></div><div id="bk_toc_contnr"></div></div></div>
|
||
<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK143562</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/23762953" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">23762953</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/mlprobe/">Contents</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/mlprobe/ml262/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/mlprobe/ml258/" title="Next page in this title">Next ></a></div></div></div></div>
|
||
|
||
</div>
|
||
|
||
<!-- Custom content below content -->
|
||
<div class="col4">
|
||
|
||
</div>
|
||
|
||
|
||
<!-- Book content -->
|
||
|
||
<!-- Custom contetnt below bottom nav -->
|
||
<div class="col5">
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div id="rightcolumn" class="four_col col last">
|
||
<!-- Custom content above discovery portlets -->
|
||
<div class="col6">
|
||
<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK143562&db=books">Share</a></div>
|
||
|
||
</div>
|
||
<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK143562/?report=reader">PubReader</a></li><li><a href="/books/NBK143562/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK143562" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK143562" style="display:none" title="Cite this Page"><div class="bk_tt">Ganji S, Zou J, Brown B, et al. A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor. 2011 Oct 31 [Updated 2013 Mar 7]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. <span class="bk_cite_avail"></span></div></div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#ml260.s1" ref="log$=inpage&link_id=inpage">Probe Structure & Characteristics</a></li><li><a href="#ml260.s2" ref="log$=inpage&link_id=inpage">Recommendations for Scientific Use of the Probe</a></li><li><a href="#ml260.s3" ref="log$=inpage&link_id=inpage">Materials and Methods</a></li><li><a href="#ml260.s13" ref="log$=inpage&link_id=inpage">Results</a></li><li><a href="#ml260.s17" ref="log$=inpage&link_id=inpage">Discussion</a></li><li><a href="#ml260.s19" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=3036550" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcassay&DbFrom=books&Cmd=Link&LinkName=books_pcassay_probe&IdsFromResult=3036550" ref="log$=recordlinks">PubChem BioAssay for Chemical Probe</a><div class="brieflinkpop offscreen_noflow">PubChem BioAssay records reporting screening data for the development of the chemical probe(s) described in this book chapter</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pcsubstance&DbFrom=books&Cmd=Link&LinkName=books_pcsubstance&IdsFromResult=3036550" ref="log$=recordlinks">PubChem Substance</a><div class="brieflinkpop offscreen_noflow">Related PubChem Substances</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=3036550" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/23860652" ref="ordinalpos=1&linkpos=1&log$=relatedarticles&logdbfrom=pubmed">Modulators of intestinal alkaline phosphatase.</a><span class="source">[Methods Mol Biol. 2013]</span><div class="brieflinkpop offscreen_noflow">Modulators of intestinal alkaline phosphatase.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Bobkova EV, Kiffer-Moreira T, Sergienko EA. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Methods Mol Biol. 2013; 1053:135-44. </em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/24412070" ref="ordinalpos=1&linkpos=2&log$=relatedarticles&logdbfrom=pubmed">Identification of a selective inhibitor of murine intestinal alkaline phosphatase (ML260) by concurrent ultra-high throughput screening against human and mouse isozymes.</a><span class="source">[Bioorg Med Chem Lett. 2014]</span><div class="brieflinkpop offscreen_noflow">Identification of a selective inhibitor of murine intestinal alkaline phosphatase (ML260) by concurrent ultra-high throughput screening against human and mouse isozymes.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Ardecky RJ, Bobkova EV, Kiffer-Moreira T, Brown B, Ganji S, Zou J, Pass I, Narisawa S, Iano FG, Rosenstein C, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Bioorg Med Chem Lett. 2014 Feb 1; 24(3):1000-1004. Epub 2013 Dec 19.</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21433367" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2.</a><span class="source">[Probe Reports from the NIH Mol...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 2.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lanier M, Cashman J, Sergienko E, Garcia X, Brown B, Rascon J, Narisawa S, Simao AM, Millán JL, Stonich D, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Probe Reports from the NIH Molecular Libraries Program. 2010</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/21433359" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1.</a><span class="source">[Probe Reports from the NIH Mol...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Placental Alkaline Phosphatase (PLAP) Luminescent HTS assay - Probe 1.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Sergienko E, Garcia X, Brown B, Rascon J, Narisawa S, Simao AM, Millán JL, Stonich D, Su Y, Khan P, et al. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">Probe Reports from the NIH Molecular Libraries Program. 2010</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/12372831" ref="ordinalpos=1&linkpos=5&log$=relatedarticles&logdbfrom=pubmed">Structural evidence of functional divergence in human alkaline phosphatases.</a><span class="source">[J Biol Chem. 2002]</span><div class="brieflinkpop offscreen_noflow">Structural evidence of functional divergence in human alkaline phosphatases.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Le Du MH, Millan JL. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">J Biol Chem. 2002 Dec 20; 277(51):49808-14. Epub 2002 Oct 7.</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=23762953" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=23762953" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d66b9784f3725e592c1ab4">A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor - Probe Rep...</a><div class="ralinkpop offscreen_noflow">A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d66b9667c23b31e0b1ec0b">Potent inhibitors of lipid droplet formation - Probe Reports from the NIH Molecu...</a><div class="ralinkpop offscreen_noflow">Potent inhibitors of lipid droplet formation - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d66b95cde49f3df7db07d5">ML264: An Antitumor Agent that Potently and Selectively Inhibits Krüppel-like Fa...</a><div class="ralinkpop offscreen_noflow">ML264: An Antitumor Agent that Potently and Selectively Inhibits Krüppel-like Factor Five (KLF5) Expression: A Probe for Studying Colon Cancer Development and Progression - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d66b9484f3725e592c0ce1">ML265: A potent PKM2 activator induces tetramerization and reduces tumor formati...</a><div class="ralinkpop offscreen_noflow">ML265: A potent PKM2 activator induces tetramerization and reduces tumor formation and size in a mouse xenograft model - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d66b9384f3725e592c0874">Discovery, SAR, and Biological Evaluation of Non-inhibitory Chaperones of Glucoc...</a><div class="ralinkpop offscreen_noflow">Discovery, SAR, and Biological Evaluation of Non-inhibitory Chaperones of Glucocerebrosidase - Probe Reports from the NIH Molecular Libraries Program<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
|
||
|
||
<!-- Custom content below discovery portlets -->
|
||
<div class="col7">
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<!-- Custom content after all -->
|
||
<div class="col8">
|
||
|
||
</div>
|
||
<div class="col9">
|
||
|
||
</div>
|
||
|
||
<script type="text/javascript" src="/corehtml/pmc/js/jquery.scrollTo-1.4.2.js"></script>
|
||
<script type="text/javascript">
|
||
(function($){
|
||
$('.skiplink').each(function(i, item){
|
||
var href = $($(item).attr('href'));
|
||
href.attr('tabindex', '-1').addClass('skiptarget'); // ensure the target can receive focus
|
||
$(item).on('click', function(event){
|
||
event.preventDefault();
|
||
$.scrollTo(href, 0, {
|
||
onAfter: function(){
|
||
href.focus();
|
||
}
|
||
});
|
||
});
|
||
});
|
||
})(jQuery);
|
||
</script>
|
||
</div>
|
||
<div class="bottom">
|
||
|
||
<div id="NCBIFooter_dynamic">
|
||
<!--<component id="Breadcrumbs" label="breadcrumbs"/>
|
||
<component id="Breadcrumbs" label="helpdesk"/>-->
|
||
|
||
</div>
|
||
|
||
<div class="footer" id="footer">
|
||
<section class="icon-section">
|
||
<div id="icon-section-header" class="icon-section_header">Follow NCBI</div>
|
||
<div class="grid-container container">
|
||
<div class="icon-section_container">
|
||
<a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11 {
|
||
fill: #737373;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>Twitter</title>
|
||
<path class="cls-11" d="M250.11,105.48c-7,3.14-13,3.25-19.27.14,8.12-4.86,8.49-8.27,11.43-17.46a78.8,78.8,0,0,1-25,9.55,39.35,39.35,0,0,0-67,35.85,111.6,111.6,0,0,1-81-41.08A39.37,39.37,0,0,0,81.47,145a39.08,39.08,0,0,1-17.8-4.92c0,.17,0,.33,0,.5a39.32,39.32,0,0,0,31.53,38.54,39.26,39.26,0,0,1-17.75.68,39.37,39.37,0,0,0,36.72,27.3A79.07,79.07,0,0,1,56,223.34,111.31,111.31,0,0,0,116.22,241c72.3,0,111.83-59.9,111.83-111.84,0-1.71,0-3.4-.1-5.09C235.62,118.54,244.84,113.37,250.11,105.48Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>Facebook</title>
|
||
<path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>LinkedIn</title>
|
||
<path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11,
|
||
.cls-12 {
|
||
fill: #737373;
|
||
}
|
||
|
||
.cls-11 {
|
||
fill-rule: evenodd;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>GitHub</title>
|
||
<path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z">
|
||
</path>
|
||
<path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1">
|
||
</path>
|
||
<path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08">
|
||
</path>
|
||
<path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path>
|
||
<path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog">
|
||
<svg xmlns="http://www.w3.org/2000/svg" id="Layer_1" data-name="Layer 1" viewBox="0 0 40 40">
|
||
<defs><style>.cls-1{fill:#737373;}</style></defs>
|
||
<title>NCBI Insights Blog</title>
|
||
<path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"></path>
|
||
</svg>
|
||
</a>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
|
||
<section class="container-fluid bg-primary">
|
||
<div class="container pt-5">
|
||
<div class="row mt-3">
|
||
<div class="col-lg-3 col-12">
|
||
<p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p>
|
||
<ul class="list-inline social_media">
|
||
<li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st20 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st30 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Twitter</title>
|
||
<g>
|
||
<g>
|
||
<g>
|
||
<path class="st20" d="M192.9,88.1c-5,2.2-9.2,2.3-13.6,0.1c5.7-3.4,6-5.8,8.1-12.3c-5.4,3.2-11.4,5.5-17.6,6.7 c-10.5-11.2-28.1-11.7-39.2-1.2c-7.2,6.8-10.2,16.9-8,26.5c-22.3-1.1-43.1-11.7-57.2-29C58,91.6,61.8,107.9,74,116 c-4.4-0.1-8.7-1.3-12.6-3.4c0,0.1,0,0.2,0,0.4c0,13.2,9.3,24.6,22.3,27.2c-4.1,1.1-8.4,1.3-12.5,0.5c3.6,11.3,14,19,25.9,19.3 c-11.6,9.1-26.4,13.2-41.1,11.5c12.7,8.1,27.4,12.5,42.5,12.5c51,0,78.9-42.2,78.9-78.9c0-1.2,0-2.4-0.1-3.6 C182.7,97.4,189.2,93.7,192.9,88.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st30" cx="124.4" cy="128.8" r="108.2"></circle>
|
||
</g>
|
||
</svg></a></li>
|
||
<li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank">
|
||
<svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st10 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st110 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Facebook</title>
|
||
<g>
|
||
<g>
|
||
<path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle>
|
||
</svg>
|
||
</a></li>
|
||
<li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<title>Youtube</title>
|
||
<style type="text/css">
|
||
.st4 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
|
||
.st5 {
|
||
fill: #FFFFFF;
|
||
}
|
||
</style>
|
||
<circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle>
|
||
<g transform="translate(0,-952.36218)">
|
||
<path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path>
|
||
</g>
|
||
</svg></a></li>
|
||
</ul>
|
||
</div>
|
||
<div class="col-lg-3 col-12">
|
||
<p class="address_footer text-white">National Library of Medicine<br />
|
||
<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
|
||
Bethesda, MD 20894</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
|
||
<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
|
||
<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
|
||
<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
|
||
<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
|
||
</div>
|
||
</div>
|
||
<div class="row">
|
||
<div class="col-lg-12 centered-lg">
|
||
<nav class="bottom-links">
|
||
<ul class="mt-3">
|
||
<li>
|
||
<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.nih.gov/">NIH</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.hhs.gov/">HHS</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
|
||
</li>
|
||
</ul>
|
||
</nav>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentOmnitureBaseJS/InstrumentNCBIConfigJS/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js?v=1"> </script>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/static/js/hfjs2.js"> </script>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<!--/.page-->
|
||
</div>
|
||
<!--/.wrap-->
|
||
</div><!-- /.twelve_col -->
|
||
</div>
|
||
<!-- /.grid -->
|
||
|
||
<span class="PAFAppResources"></span>
|
||
|
||
<!-- BESelector tab -->
|
||
|
||
|
||
|
||
<noscript><img alt="statistics" src="/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK143562&ncbi_domain=mlprobe&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK143562/&ncbi_pagename=A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor - Probe Reports from the NIH Molecular Libraries Program - NCBI Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf" /></noscript>
|
||
|
||
|
||
<!-- usually for JS scripts at page bottom -->
|
||
<!--<component id="PageFixtures" label="styles"></component>-->
|
||
|
||
|
||
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal107 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
||
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
||
|
||
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3879255/4121861/3501987/4008961/3893018/3821238/4062932/4209313/4212053/4076480/3921943/3400083/3426610.js" snapshot="books"></script></body>
|
||
</html> |