{"id":1495,"date":"2023-01-19T14:43:59","date_gmt":"2023-01-19T06:43:59","guid":{"rendered":"http:\/\/www.biocloudservice.com\/wordpress\/?p=1495"},"modified":"2023-01-19T14:43:59","modified_gmt":"2023-01-19T06:43:59","slug":"discovery-of-potent-selective-orally-bioavailable-stearoyl-coa-desaturase-1-inhibitors","status":"publish","type":"post","link":"http:\/\/www.biocloudservice.com\/wordpress\/?p=1495","title":{"rendered":"Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors."},"content":{"rendered":"<p>Research |Published:2008-9-3\u00a0 | ISSN:0022-2623\u00a0 |doi:10.1021\/jm070219p |pmid:17530838<\/p>\n<hr \/>\n<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Abstract<\/h2>\n<hr \/>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.<\/p>\n<hr \/>\n<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">\u53d1\u73b0\u6709\u6548\u7684\u3001\u9009\u62e9\u6027\u7684\u3001\u53e3\u670d\u751f\u7269\u53ef\u5229\u7528\u7684\u786c\u8102\u9170\u8f85\u9176a\u53bb\u9971\u548c\u91761\u6291\u5236\u5242\u3002<\/h2>\n<hr \/>\n<p>\u786c\u8102\u9170\u8f85\u9176a\u53bb\u9971\u548c\u91761 (SCD1)\u50ac\u5316\u4ece\u9971\u548c\u957f\u94fe\u8102\u80aa\u9178\u751f\u7269\u5408\u6210\u5355\u4e0d\u9971\u548c\u8102\u80aa\u9178\u7684\u5173\u952e\u6b65\u9aa4\u3002\u5bf9SCD1\u57fa\u56e0\u6572\u9664\u5c0f\u9f20\u7684\u7814\u7a76\u5df2\u7ecf\u8bc1\u5b9e\uff0c\u8fd9\u4e9b\u52a8\u7269\u662f\u7626\u7684\uff0c\u4e0d\u53d7\u7626\u7d20\u7f3a\u4e4f\u8bf1\u5bfc\u7684\u548c\u996e\u98df\u8bf1\u5bfc\u7684\u80a5\u80d6\u7684\u5f71\u54cd\uff0c\u6bd4\u91ce\u751f\u578b\u52a8\u7269\u5177\u6709\u66f4\u9ad8\u7684\u5168\u8eab\u80f0\u5c9b\u7d20\u654f\u611f\u6027\u3002\u5728\u8fd9\u9879\u5de5\u4f5c\u4e2d\uff0c\u6211\u4eec\u53d1\u73b0\u4e86\u4e00\u7cfb\u5217\u57fa\u4e8e\u5df2\u77e5\u54d2\u55ea\u7532\u9170\u80fa\u6a21\u677f\u7684\u6709\u6548\u3001\u9009\u62e9\u6027\u3001\u53e3\u670d\u751f\u7269\u5229\u7528\u7684SCD1\u6291\u5236\u5242\u3002\u4ee3\u8868\u6027\u7684\u94c5\u6291\u5236\u524228c\u4e5f\u8bc1\u660e\u4e86\u5728HepG2\u7ec6\u80de\u4e2d\u963b\u65ad\u9971\u548c\u957f\u94fe\u8102\u80aa\u9178\u8f85\u9176a(LCFA \u8f85\u9176a)\u8f6c\u5316\u4e3a\u5355\u4e0d\u9971\u548cLCFA \u8f85\u9176a\u7684\u4f18\u5f02\u7ec6\u80de\u6d3b\u6027\u3002<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Research |Published:2008-9-3\u00a0 | ISSN:0022-2623\u00a0 |doi:10 [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":""},"categories":[],"tags":[],"jetpack_featured_media_url":"","_links":{"self":[{"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1495"}],"collection":[{"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1495"}],"version-history":[{"count":0,"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1495\/revisions"}],"wp:attachment":[{"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1495"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1495"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.biocloudservice.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1495"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}