{"id":11897,"date":"2020-11-30T07:07:00","date_gmt":"2020-11-30T00:07:00","guid":{"rendered":"https:\/\/www.xinwengao.com\/cn\/pr\/2020113007070011897"},"modified":"2020-11-30T09:13:30","modified_gmt":"2020-11-30T01:13:30","slug":"%e4%ba%9a%e7%9b%9b%e5%8c%bb%e8%8d%af%e4%b8%8e%e5%af%86%e8%a5%bf%e6%a0%b9%e5%a4%a7%e5%ad%a6%e8%be%be%e6%88%90%e5%8d%8f%e8%ae%ae%ef%bc%8c%e8%8e%b7%e5%be%97%e5%9f%ba%e4%ba%8eprotac%e6%8a%80%e6%9c%af","status":"publish","type":"post","link":"https:\/\/www.xinwengao.com\/cn\/pr\/2020113007070011897","title":{"rendered":"\u4e9a\u76db\u533b\u836f\u4e0e\u5bc6\u897f\u6839\u5927\u5b66\u8fbe\u6210\u534f\u8bae\uff0c\u83b7\u5f97\u57fa\u4e8ePROTAC\u6280\u672f\u7684MDM2\u86cb\u767d\u964d\u89e3\u5242\u7684\u72ec\u5bb6\u8bb8\u53ef"},"content":{"rendered":"<table border=\"0\" cellspacing=\"10\" cellpadding=\"5\" align=\"right\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" src=\"https:\/\/www.xinwengao.com\/cn\/wp-content\/uploads\/Ascentage_Pharma_Logo.jpg\" border=\"0\" alt=\"\" title=\"logo\" hspace=\"0\" vspace=\"0\" width=\"118\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><p>\u4e2d\u56fd\u82cf\u5dde\u548c\u7f8e\u56fd\u9a6c\u91cc\u5170\u5dde\u7f57\u514b\u7ef4\u5c14\u5e022020\u5e7412\u670830\u65e5 \/\u7f8e\u901a\u793e\/ &#8212; \u81f4\u529b\u4e8e\u5728\u80bf\u7624\u3001\u4e59\u809d\u53ca\u4e0e\u8870\u8001\u76f8\u5173\u75be\u75c5\u7b49\u6cbb\u7597\u9886\u57df\u5f00\u53d1\u521b\u65b0\u836f\u7269\u7684\u5904\u4e8e\u4e34\u5e8a\u9636\u6bb5\u7684\u7814\u53d1\u4f01\u4e1a &#8212; \u4e9a\u76db\u533b\u836f\uff086855.HK\uff09\u4eca\u65e5\u5ba3\u5e03\uff0c\u516c\u53f8\u4e0e\u5bc6\u897f\u6839\u5927\u5b66\u8fbe\u6210\u534f\u8bae\uff0c\u5c06\u83b7\u5f97\u4e00\u9879\u57fa\u4e8e\u86cb\u767d\u964d\u89e3\u9776\u5411\u5d4c\u5408\u4f53(Proteolysis-Targeting Chimeras, PROTACs)\u6280\u672f\u5f00\u53d1\u7684MDM2\u86cb\u767d\u964d\u89e3\u5242\u7684\u5168\u7403\u72ec\u5bb6\u6743\u76ca\u3002\u8be5\u4e34\u5e8a\u5019\u9009\u7269\u5df2\u8fdb\u5165IND\u7533\u62a5\u8bd5\u9a8c\u9636\u6bb5\u3002<\/p>\n<p>MDM2\u662f\u80bf\u7624\u6291\u5236\u56e0\u5b50p53\u7684\u5173\u952e\u8d1f\u8c03\u8282\u56e0\u5b50\uff0c\u662f\u8fc4\u4eca\u4e3a\u6b62\u53d1\u73b0\u7684\u6700\u5f3a\u7684\u51cb\u4ea1\u6291\u5236\u56e0\u5b50\u4e4b\u4e00\uff0c\u5728\u80bf\u7624\u4e2d\u9ad8\u8868\u8fbe\uff0c\u5bf9\u80bf\u7624\u7684\u53d1\u751f\u548c\u53d1\u5c55\u8d77\u5230\u91cd\u8981\u7684\u4f5c\u7528\u3002MDM2\u6291\u5236\u5242\u901a\u8fc7\u9ad8\u4eb2\u548c\u529b\u7ed3\u5408MDM2\u86cb\u767d\uff0c\u963b\u65adMDM2-p53\u76f8\u4e92\u4f5c\u7528\u4ece\u800c\u6062\u590dp53\u80bf\u7624\u6291\u5236\u6d3b\u6027<sup><span id=\"spanHghlt7339\">[1]<\/span><\/sup>\u3002\u7136\u800cMDM2\u6291\u5236\u5242\u8fd8\u5b58\u5728\u4e00\u4e9b\u95ee\u9898\uff0c\u5305\u62ec\u5242\u91cf\u53d7\u5230\u8840\u6db2\u5b66\u53ca\u76f8\u5173\u6bd2\u6027\u7684\u9650\u5236\u7b49\u3002\u56e0\u6b64\uff0c\u8feb\u5207\u9700\u8981\u5f00\u53d1\u9776\u5411MDM2\u7528\u4e8e\u80bf\u7624\u6cbb\u7597\u7684\u65b0\u7b56\u7565\u3002\u800cPROTAC\u6280\u672f\u662f\u901a\u8fc7\u6cdb\u7d20-\u86cb\u767d\u9176\u4f53\u7cfb\u7edf\uff08UPS\uff09\u8bf1\u5bfc\u9776\u5411\u86cb\u767d\u964d\u89e3\u7684\u4e00\u79cd\u5168\u65b0\u6280\u672f\u3002\u6b64\u6280\u672f\u81ea\u95ee\u4e16\u4ee5\u6765\u53d7\u5230\u6765\u81ea\u5b66\u672f\u754c\u548c\u5de5\u4e1a\u754c\u7684\u5e7f\u6cdb\u5173\u6ce8\u3002\u533a\u522b\u4e8e\u4f20\u7edf\u7684\u5360\u636e\u9a71\u52a8\uff08occupancy-driven\uff09\u7684\u836f\u7406\u5b66\u539f\u7406\uff0c\u4e8b\u4ef6\u9a71\u52a8(event-driven)\u7684PROTAC\u6280\u672f\u5177\u6709\u8bf8\u591a\u4f18\u52bf\uff0c\u6bd4\u5982\u5177\u6709\u9ad8\u6d3b\u6027\u3001\u9ad8\u9009\u62e9\u6027\uff0c\u50ac\u5316\u964d\u89e3\u4f5c\u7528\u6a21\u5f0f\uff0c\u9776\u5411\u4e0d\u53ef\u6210\u836f\u9776\u70b9\u7b49<sup><span id=\"spanHghltb96f\">[2]<\/span><\/sup>\u3002<\/p>\n<p>\u4e9a\u76db\u533b\u836f\u5171\u540c\u521b\u59cb\u4eba\u517c\u9996\u5e2d\u79d1\u5b66\u987e\u95ee\u3001\u5bc6\u897f\u6839\u5927\u5b66Warner-Lambert\/Parke-Davis\u533b\u5b66\u6559\u6388\u3001\u5185\u79d1\u6559\u6388\u3001\u836f\u7406\u5b66\u6559\u6388\u548c\u836f\u7269\u5316\u5b66\u4e13\u4e1a\u6559\u6388\u3001\u5bc6\u897f\u6839\u533b\u7597\u521b\u65b0\u4e2d\u5fc3\u4e3b\u4efb\u738b\u5c11\u840c\u535a\u58eb\u662f\u8fd9\u4e00\u7814\u53d1\u9886\u57df\u7684\u9886\u519b\u4eba\u7269\u3002\u738b\u5c11\u840c\u6559\u6388\u8bfe\u9898\u7ec4\u901a\u8fc7\u8fd0\u7528PROTAC\u6280\u672f\uff0c\u5bf9\u4ed6\u4eec\u4e4b\u524d\u5f00\u53d1\u7684MDM2\u6291\u5236\u5242\u8fdb\u884c\u7cfb\u7edf\u7684\u6784\u6548\u5173\u7cfb\u7814\u7a76\uff0c\u83b7\u5f97\u4e86\u80fd\u591f\u6709\u6548\u8bf1\u5bfcMDM2\u5feb\u901f\u964d\u89e3\u7684\u9ad8\u6548MDM2\u964d\u89e3\u5242\u3002MDM2\u964d\u89e3\u5242\u53ef\u4ee5\u5728\u5c0f\u9f20\u5f02\u79cd\u79fb\u690d\u7684\u80bf\u7624\u6a21\u578b\u4e2d\u5b8c\u5168\u5e76\u6301\u4e45\u5730\u6291\u5236\u80bf\u7624\u7684\u751f\u957f<sup><span id=\"spanHghlt2039\">[3]<\/span><\/sup>\u3002<\/p>\n<p>\u738b\u5c11\u840c\u535a\u58eb\u8868\u793a\uff1a\u201cPROTAC\u4f5c\u4e3a\u65b0\u9896\u7684\u8bf1\u5bfc\u86cb\u767d\u964d\u89e3\u65b9\u5f0f\u5df2\u6210\u4e3a\u4e00\u79cd\u5168\u65b0\u7684\u836f\u7269\u53d1\u73b0\u7b56\u7565\u3002\u7814\u7a76\u8868\u660e\uff0cPROTAC\u8bf1\u5bfcMDM2\u964d\u89e3\u4e0d\u4ec5\u53ef\u4ee5\u589e\u5f3aMDM2\u6291\u5236\u5242\u6d3b\u6027\u548c\u6709\u6548\u6027\uff0c\u800c\u4e14\u53ef\u4ee5\u7ef4\u6301MDM2\u86cb\u767d\u5904\u4e8e\u957f\u671f\u6291\u5236\u7684\u6c34\u5e73\uff0c\u6b64\u9879\u6280\u672f\u4e3a\u4e34\u5e8a\u4e0a\u6cbb\u7597MDM2\u9a71\u52a8\u7684\u767d\u8840\u75c5\u53ca\u5176\u4ed6\u7c7b\u578b\u7684\u80bf\u7624\u63d0\u4f9b\u4e86\u65b0\u7684\u7814\u7a76\u7b56\u7565\u3002\u6211\u4eec\u671f\u5f85\u4e9a\u76db\u533b\u836f\u7684\u8fdb\u4e00\u6b65\u5f00\u53d1\u3002\u201d<\/p>\n<p>\u4e9a\u76db\u533b\u836f\u8463\u4e8b\u957f\u6768\u5927\u4fca\u535a\u58eb\u8868\u793a\uff1a\u201cROTAC\u6280\u672f\u7684\u5174\u8d77\u4e0e\u7a81\u7834\u662f\u5c0f\u5206\u5b50\u836f\u7269\u7814\u53d1\u7684\u53c8\u4e00\u9769\u547d\u6027\u8fdb\u5c55\uff0c\u8be5\u6280\u672f\u4ee5\u5176\u53ef\u9776\u5411\u4f20\u7edf\u201c\u4e0d\u53ef\u6210\u836f\u201d\u86cb\u767d\u7684\u72ec\u7279\u4f18\u52bf\u800c\u5907\u53d7\u4e1a\u754c\u5173\u6ce8\u3002\u6211\u4eec\u5f88\u9ad8\u5174\u4e0e\u5bc6\u897f\u6839\u5927\u5b66\u8fbe\u6210\u6b64\u9879\u534f\u8bae\uff0c\u4ece\u800c\u6d89\u8db3\u57fa\u4e8ePROTAC\u6280\u672f\u7684MDM2\u86cb\u767d\u964d\u89e3\u5242\u7814\u53d1\u7684\u65b0\u5174\u9886\u57df\uff0c\u4e5f\u662f\u5bf9\u4e9a\u76db\u73b0\u6709\u4ea7\u54c1\u7ebf\u7684\u91cd\u8981\u6269\u5145\u3002\u6211\u4eec\u5c06\u52a0\u5feb\u5bf9\u8fd9\u4e00MDM2\u86cb\u767d\u964d\u89e3\u5242\u7684\u7814\u7a76\u53ca\u5f00\u53d1\uff0c\u65e9\u65e5\u4e3a\u5c1a\u672a\u6ee1\u8db3\u3001\u6025\u9700\u7684\u4e34\u5e8a\u9700\u6c42\u63d0\u4f9b\u6709\u6548\u7684\u6cbb\u7597\u9009\u62e9\u3002\u201d<\/p>\n<div>\n<table id=\"convertedTable2dbf\" cellspacing=\"0\" cellpadding=\"0\" border=\"1\" class=\"prntblns\">\n<tbody>\n<tr>\n<td class=\"prngen2\">\n<p class=\"prnews_p\"><span class=\"prnews_span\"><b>\u53c2\u8003\u8d44\u6599<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td class=\"prngen2\">\n<p class=\"prnews_p\"><span class=\"prnews_span\"><sup>[1].<\/sup> Zhao, Y.; Aguilar, A.; Bernard, D.; Wang, S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment. <i>J. Med. Chem<\/i>. 2015, <i>58<\/i>, 1038\u22121052.<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td class=\"prngen2\">\n<p class=\"prnews_p\"><span class=\"prnews_span\"><sup>[2].<\/sup> Lai, A. C.; Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. <i>Nat Rev. Drug Discov. <\/i>2017, <i>16<\/i>, 101-114.<\/span><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td class=\"prngen2\">\n<p class=\"prnews_p\"><span class=\"prnews_span\"><sup>[3].<\/sup> Ryan P. Wurz&nbsp;and Victor J. Cee. Targeted Degradation of MDM2 as a New Approach to Improve the Efficacy of MDM2-p53 Inhibitors. <i>J. Med. Chem<\/i>. 2019, <i>62<\/i>, 445\u2212447.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table><\/div>\n<p><b>\u5173\u4e8e\u4e9a\u76db\u533b\u836f<\/b><\/p>\n<p>\u4e9a\u76db\u533b\u836f\u662f\u4e00\u5bb6\u7acb\u8db3\u4e2d\u56fd\u3001\u9762\u5411\u5168\u7403\u7684\u5904\u4e8e\u4e34\u5e8a\u5f00\u53d1\u9636\u6bb5\u7684\u539f\u521b\u65b0\u836f\u7814\u53d1\u4f01\u4e1a\uff0c\u81f4\u529b\u4e8e\u5728\u80bf\u7624\u3001\u4e59\u809d\u53ca\u4e0e\u8870\u8001\u76f8\u5173\u7684\u75be\u75c5\u7b49\u6cbb\u7597\u9886\u57df\u5f00\u53d1\u521b\u65b0\u836f\u7269\u30022019\u5e7410\u670828\u65e5\uff0c\u4e9a\u76db\u533b\u836f\u5728\u9999\u6e2f\u8054\u4ea4\u6240\u4e3b\u677f\u6302\u724c\u4e0a\u5e02\uff0c\u80a1\u7968\u4ee3\u7801\uff1a6855.HK\u3002<\/p>\n<p>\u4e9a\u76db\u533b\u836f\u62e5\u6709\u81ea\u4e3b\u6784\u5efa\u7684\u86cb\u767d-\u86cb\u767d\u76f8\u4e92\u4f5c\u7528\u9776\u5411\u836f\u7269\u8bbe\u8ba1\u5e73\u53f0\uff0c\u5904\u4e8e\u7ec6\u80de\u51cb\u4ea1\u901a\u8def\u65b0\u836f\u7814\u53d1\u7684\u5168\u7403\u6700\u524d\u6cbf\u3002\u516c\u53f8\u5df2\u5efa\u7acb\u62e5\u67098\u4e2a\u5df2\u8fdb\u5165\u4e34\u5e8a\u5f00\u53d1\u9636\u6bb5\u76841\u7c7b\u5c0f\u5206\u5b50\u65b0\u836f\u4ea7\u54c1\u7ba1\u7ebf\uff0c\u5305\u62ec\u6291\u5236Bcl-2\u3001IAP \u6216 MDM2-p53 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:<\/p>\n<blockquote class=\"wp-embedded-content\" data-secret=\"knTy3TIO9Q\"><p><a href=\"https:\/\/www.ascentagepharma.com\/\">A Leader in the Discovery and Development of Small Molecules that Disrupt Protein-Protein Interactions<\/a><\/p><\/blockquote>\n<p><iframe class=\"wp-embedded-content\" sandbox=\"allow-scripts\" security=\"restricted\" style=\"position: absolute; clip: rect(1px, 1px, 1px, 1px);\" title=\"&#8220;A Leader in the Discovery and Development of Small Molecules that Disrupt Protein-Protein Interactions&#8221; &#8212; Ascentage Pharma\" src=\"https:\/\/www.ascentagepharma.com\/embed\/#?secret=knTy3TIO9Q\" data-secret=\"knTy3TIO9Q\" width=\"600\" height=\"338\" frameborder=\"0\" marginwidth=\"0\" marginheight=\"0\" scrolling=\"no\"><\/iframe><\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u4e2d\u56fd\u82cf\u5dde\u548c\u7f8e\u56fd\u9a6c\u91cc\u5170\u5dde\u7f57\u514b\u7ef4\u5c14\u5e022020\u5e7412\u670830\u65e5 \/\u7f8e\u901a\u793e\/ &#8212; 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\u53c2\u8003\u8d44\u6599 [1]. Zhao, Y.; Aguilar, A.; Bernard, D.; Wang, S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment. J. Med. Chem. 2015, 58, 1038\u22121052. [2]. Lai, A. C.; Crews, C. M. Induced protein degradation: an emerging&hellip; <a class=\"read-more\" href=\"https:\/\/www.xinwengao.com\/cn\/pr\/2020113007070011897\">Read More<\/a><\/p>\n","protected":false},"author":556,"featured_media":11901,"comment_status":"close","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1965],"tags":[],"class_list":["post-11897","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-partnerships"],"amp_enabled":true,"_links":{"self":[{"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/posts\/11897","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/users\/556"}],"replies":[{"embeddable":true,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/comments?post=11897"}],"version-history":[{"count":1,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/posts\/11897\/revisions"}],"predecessor-version":[{"id":11900,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/posts\/11897\/revisions\/11900"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/media\/11901"}],"wp:attachment":[{"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/media?parent=11897"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/categories?post=11897"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.xinwengao.com\/cn\/wp-json\/wp\/v2\/tags?post=11897"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}