{"id":1120,"date":"2022-07-10T16:28:38","date_gmt":"2022-07-10T08:28:38","guid":{"rendered":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1120"},"modified":"2022-07-11T10:01:32","modified_gmt":"2022-07-11T02:01:32","slug":"%e4%b8%80%e7%b1%bb%e6%96%b0%e5%9e%8b%e5%a4%a7%e7%8e%af%e7%b1%bb-pim-1-%e6%bf%80%e9%85%b6%e6%8a%91%e5%88%b6%e5%89%82%e7%9a%84%e8%ae%be%e8%ae%a1%e3%80%81%e5%90%88%e6%88%90%e5%8f%8a%e7%94%9f%e7%89%a9","status":"publish","type":"post","link":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1120","title":{"rendered":"\u4e00\u7c7b\u65b0\u578b\u5927\u73af\u7c7b Pim-1 \u6fc0\u9176\u6291\u5236\u5242\u7684\u8bbe\u8ba1\u3001\u5408\u6210\u53ca\u751f\u7269\u6d3b\u6027\u8bc4\u4f30"},"content":{"rendered":"\n<p><\/p>\n\n\n\n<pre class=\"wp-block-code\"><code><\/code><\/pre>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><a href=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc.jpg\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc-1024x666.jpg\" alt=\"\" class=\"wp-image-1117\" width=\"328\" height=\"213\" srcset=\"https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc-1024x666.jpg 1024w, https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc-300x195.jpg 300w, https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc-768x500.jpg 768w, https:\/\/www.huanglab.org.cn\/wordpress\/wp-content\/uploads\/2022\/07\/sc.jpg 1362w\" sizes=\"auto, (max-width: 328px) 100vw, 328px\" \/><\/a><\/figure>\n\n\n\n<p>\u3000\u30002022\u5e747\u67082\u65e5\uff0c\u5317\u4eac\u751f\u547d\u79d1\u5b66\u7814\u7a76\u6240\/\u6e05\u534e\u5927\u5b66\u751f\u7269\u533b\u5b66\u4ea4\u53c9\u7814\u7a76\u9662\u200b\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u4e0e\u5317\u4eac\u5316\u5de5\u5927\u5b66\u90d1\u56fd\u5747\u8bfe\u9898\u7ec4\u5408\u4f5c\uff0c\u5728\u671f\u520a\u200b <a rel=\"noreferrer noopener\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0960894X2200350X?dgcid=coauthor\" data-type=\"URL\" data-id=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0960894X2200350X?dgcid=coauthor\" target=\"_blank\">Bioorganic &amp; Medicinal Chemistry Letters \u53d1\u8868\u4e86\u6587\u7ae0 Design, synthesis, and bioactivity evaluation of macrocyclic benzo[b]pyrido[4,3-e][1,4]oxazine derivatives as novel Pim-1 kinase inhibitors<\/a>\uff0c \u53d1\u73b0\u4e00\u7c7b\u65b0\u578b\u7684\u5927\u73af\u7c7b Pim-1 \u6fc0\u9176\u6291\u5236\u5242\uff0c\u5e76\u7ed3\u5408\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u548c\u6676\u4f53\u5b66\u624b\u6bb5\u5bf9\u7ed3\u5408\u6a21\u5f0f\u8fdb\u884c\u4e86\u63a2\u7a76\u3002<\/p>\n\n\n\n<pre class=\"wp-block-code\"><code>    Pim-1 \u6fc0\u9176\u662f\u4e00\u79cd\u4e1d\u6c28\u9178\/\u82cf\u6c28\u9178\u6fc0\u9176\uff0c\u5728\u8bb8\u591a\u80bf\u7624\u4e2d\u8d77\u91cd\u8981\u4f5c\u7528\u3002\u524d\u671f\u5de5\u4f5c\u4e2d\uff0c\u9ec4\u725b\u56e2\u961f\u8054\u5408\u90d1\u56fd\u5747\u56e2\u961f\u53d1\u73b0\u4e86 Pim-1 \u6291\u5236\u5242 10-DEBC \u53ca\u5176\u884d\u751f\u7269\uff0c\u5177\u6709\u8f83\u9ad8\u7684\u6291\u5236\u6d3b\u6027\u3002\u5e0c\u671b\u200b\u5728\u6b64\u57fa\u7840\u4e0a\uff0c\u8fdb\u4e00\u6b65\u5f00\u53d1\u9aa8\u67b6\u65b0\u9896\u3001\u7269\u7406\u5316\u5b66\u6027\u8d28\uff08\u5982\u819c\u901a\u900f\u6027\uff09\u66f4\u4f18\u7684\u6291\u5236\u5242\u3002\n\n    \u200b\u5927\u73af\u5316\u5408\u7269\u662f\u5177\u6709\u5341\u4e8c\u4e2a\u6216\u66f4\u591a\u539f\u5b50\u7684\u5927\u73af\u7684\u5206\u5b50\uff0c\u5728\u5c0f\u5206\u5b50\u836f\u7269\u7684\u7814\u7a76\u4e2d\u5f15\u8d77\u4e86\u5f88\u591a\u5173\u6ce8\u3002\u5927\u73af\u5316\u5bf9PK\/PD\u3001\u6548\u529b\u548c\u9776\u6807\u9009\u62e9\u6027\u6709\u663e\u8457\u5f71\u54cd\uff0c\u63d0\u4f9b\u4e86\u6539\u5584\u5316\u5408\u7269\u6548\u529b\u3001\u9009\u62e9\u6027\u3001\u819c\u901a\u900f\u6027\u548c\u5176\u4ed6\u76f8\u5173\u7269\u7406\u5316\u5b66\u6027\u8d28\u7684\u673a\u4f1a\u3002\u200b\u6839\u636e\u5927\u73af\u5316\u7684\u8bbe\u8ba1\u601d\u8def\uff0c\u53c2\u8003 Pim-1 \u6fc0\u9176\u4e0e 10-DEBC \u53ca\u5176\u884d\u751f\u5316\u5408\u7269 26 \u7684\u590d\u5408\u7269\u6676\u4f53\u7ed3\u6784\uff0c\u786e\u5b9a\u4e86\u5206\u5b50\u5185\u73af\u5316\u7684\u4f4d\u70b9\u3002\u7528\u4e8e\u73af\u5316\u7684\u8fde\u63a5\u7247\u6bb5\u53ef\u7528\u4e8e\u63a2\u7d22\u9776\u70b9\u94f0\u94fe\u533a\u548c\u76f8\u90bb\u6b8b\u57fa\u5468\u56f4\u5f62\u6210\u7684\u758f\u6c34\u7a7a\u95f4\u3002\u901a\u8fc7\u91c7\u7528\u4e0d\u540c\u957f\u5ea6\u548c\u7c7b\u578b\u7684\u8fde\u63a5\u7247\u6bb5\uff0c\u8bbe\u8ba1\u4e86\u591a\u79cd benzo&#91;b]pyridine&#91;4,3\u2013e]&#91;1,4]oxazine \u5927\u73af\u5316\u5408\u7269\u3002\u5408\u6210\u5de5\u4f5c\u7531\u90d1\u56fd\u5747\u56e2\u961f\u5b8c\u6210\u3002\n\n    \u4e3a\u4e86\u63a2\u7a76\u5927\u73af\u5316\u5408\u7269\u7684\u7ed3\u5408\u6a21\u5f0f\uff0c\u4f7f\u7528 GROMACS \u7a0b\u5e8f\u8fdb\u884c\u4e86\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u3002\u5927\u73af\u5206\u5b50\u96be\u4ee5\u8fdb\u884c\u5145\u5206\u5408\u7406\u7684\u6784\u8c61\u91c7\u6837\uff0c\u8003\u8651\u5230 RDKit \u4e2d\u5b9e\u73b0\u7684 ETKDG \u65b9\u6cd5\u80fd\u591f\u59a5\u5584\u5904\u7406\u5927\u73af\u5206\u5b50\u7684\u4e8c\u9762\u89d2\u626d\u8f6c\u52bf\u80fd\uff0c\u6a21\u62df\u524d\u4f7f\u7528\u8be5\u7b97\u6cd5\u5bf9\u5927\u73af\u5206\u5b50\u7684\u4e09\u7ef4\u7ed3\u6784\u8fdb\u884c\u4e86\u5efa\u6a21\u3002\u5316\u5408\u7269 H3 \u7684\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u7ed3\u679c\u663e\u793a\uff0c\u5176\u5728 Pim-1 \u7ed3\u5408\u53e3\u888b\u4e2d\u4fdd\u6301\u7a33\u5b9a\u7684\u7ed3\u5408\u6784\u8c61\uff0c\u8868\u660e\u4e0e\u7ed3\u5408\u4f4d\u70b9\u6b8b\u57fa\u5f62\u6210\u4e86\u826f\u597d\u7684\u76f8\u4e92\u4f5c\u7528\u3002\n\n    \u6fc0\u9176\u6d3b\u6027\u8bd5\u9a8c\u7ed3\u679c\u8868\u660e\uff0c\u5927\u73af\u5316\u5408\u7269 H3\u3001H5 \u548c H10 \u5177\u6709\u8f83\u9ad8\u7684\u6291\u5236\u6d3b\u6027\uff08IC50 &lt; 100 nM\uff09\uff0c\u5176\u4e2d\u5316\u5408\u7269 H5 \u7684 IC50 \u8fbe\u5230\u4e86 35 nM\u3002\u89e3\u6790\u83b7\u5f97\u7684 Pim-1 \u6fc0\u9176\u4e0e\u5316\u5408\u7269 H3 \u7684\u590d\u5408\u7269\u6676\u4f53\u7ed3\u6784\u663e\u793a\uff0c\u5316\u5408\u7269 H3 \u7684\u200b\u6676\u4f53\u5b66\u7ed3\u5408\u6a21\u5f0f\u4e0e\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u7684\u7ed3\u679c\u57fa\u672c\u4e00\u81f4\u3002\u5177\u4f53\u800c\u8a00\uff0c\u5316\u5408\u7269 H3 \u8102\u80aa\u94fe\u4e2d\u7684\u80fa\u57fa\u4e0e Asp128 \u5f62\u6210\u76d0\u6865\u76f8\u4e92\u4f5c\u7528\uff0c\u5421\u5576\u73af\u4e2d\u7684\u6c2e\u539f\u5b50\u4e0e Lys67 \u5f62\u6210\u6c22\u952e\u76f8\u4e92\u4f5c\u7528\uff0c\u5421\u5576\u73af\u548c Phe49 \u5f62\u6210\u7684\u9762\u5bf9\u8fb9 \u03c0-\u03c0 \u76f8\u4e92\u4f5c\u7528 \uff08edge-to-face \u03c0-\u03c0 interaction\uff09\u4e5f\u88ab\u89c2\u5bdf\u5230\u3002\n\n    \u8be5\u5de5\u4f5c\u603b\u7ed3\u4e86\u4e00\u7c7b\u65b0\u578b\u5927\u73af\u5316\u5408\u7269\u7684\u7ed3\u6784\u6d3b\u6027\u5173\u7cfb\uff0c\u4e3a\u8fdb\u4e00\u6b65\u4f18\u5316  Pim-1 \u6fc0\u9176\u7684\u65b0\u578b\u5927\u73af\u6291\u5236\u5242\u63d0\u4f9b\u4e86\u575a\u5b9e\u7684\u57fa\u7840\u3002<\/code><\/pre>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u3000\u30002022\u5e747\u67082\u65e5\uff0c\u5317\u4eac\u751f\u547d\u79d1\u5b66\u7814\u7a76\u6240\/\u6e05\u534e\u5927\u5b66\u751f\u7269\u533b\u5b66\u4ea4\u53c9\u7814\u7a76\u9662\u200b\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u4e0e\u5317\u4eac\u5316\u5de5\u5927\u5b66\u90d1\u56fd\u5747\u8bfe\u9898\u7ec4\u5408\u4f5c\uff0c\u5728\u671f\u520a\u200b Bioorganic &amp; Medicinal Chemistry Letters \u53d1\u8868\u4e86\u6587\u7ae0 Design, synthesis, and bioactivity evaluation of macrocyclic benzo[b]pyrido[4,3-e][1,4]oxazine derivatives as novel Pim-1 kinase inhibitors\uff0c \u53d1\u73b0\u4e00\u7c7b\u65b0\u578b\u7684\u5927\u73af\u7c7b Pim-1 \u6fc0\u9176\u6291\u5236\u5242\uff0c\u5e76\u7ed3\u5408\u5206\u5b50\u52a8\u529b\u5b66\u6a21\u62df\u548c\u6676\u4f53\u5b66\u624b\u6bb5\u5bf9\u7ed3\u5408\u6a21\u5f0f\u8fdb\u884c\u4e86\u63a2\u7a76\u3002<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"ngg_post_thumbnail":0,"footnotes":""},"categories":[10],"tags":[],"class_list":["post-1120","post","type-post","status-publish","format-standard","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1120","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1120"}],"version-history":[{"count":8,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1120\/revisions"}],"predecessor-version":[{"id":1145,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1120\/revisions\/1145"}],"wp:attachment":[{"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1120"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1120"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.huanglab.org.cn\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1120"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}