{"id":213280,"date":"2020-11-19T08:42:13","date_gmt":"2020-11-19T00:42:13","guid":{"rendered":"http:\/\/www.cailiaoniu.com\/?p=213280"},"modified":"2020-11-19T08:42:13","modified_gmt":"2020-11-19T00:42:13","slug":"%e4%bb%8a%e6%97%a5nature%ef%bc%9a%e6%8a%97%e7%99%8c%e6%96%b0%e6%9c%ba%e5%88%b6-%e5%b0%8f%e5%88%86%e5%ad%90%e8%af%b1%e5%af%bc%e7%89%b9%e5%bc%82%e8%81%9a%e5%90%88%e5%bc%95%e5%8f%91bcl6%e9%99%8d","status":"publish","type":"post","link":"http:\/\/www.cailiaoniu.com\/?p=213280","title":{"rendered":"\u4eca\u65e5Nature\uff1a\u6297\u764c\u65b0\u673a\u5236\u2014\u5c0f\u5206\u5b50\u8bf1\u5bfc\u7279\u5f02\u805a\u5408\u5f15\u53d1BCL6\u964d\u89e3"},"content":{"rendered":"<p><strong>\u3010\u7814\u7a76\u80cc\u666f\u3011<\/strong><\/p>\n<p>\u5c0f\u5206\u5b50\u8bf1\u5bfc\u7684\u86cb\u767d\u8d28\u964d\u89e3\u5df2\u6210\u4e3a\u4e00\u79cd\u5f3a\u6709\u529b\u7684\u6cbb\u7597\u7b56\u7565\uff0c\u6709\u6548\u548c\u6301\u7eed\u5730\u6291\u5236\u975e\u9176\u4fc3\u764c\u9a71\u52a8\u86cb\u767d\u662f\u4e00\u4e2a\u4e3b\u8981\u7684\u836f\u7406\u5b66\u6311\u6218\u3002\u6c99\u5229\u5ea6\u80fa\u7c7b\u4f3c\u7269\u7684\u4e34\u5e8a\u6210\u529f\u8bc1\u660e\u4e86\u836f\u7269\u8bf1\u5bfc\u7684\u8f6c\u5f55\u56e0\u5b50\u548c\u5176\u4ed6\u764c\u75c7\u9776\u70b9\u7684\u964d\u89e3\u7684\u6cbb\u7597\u6548\u679c\uff0c\u5b83\u4eec\u53ef\u8c03\u8282CUL4-RBX1-DDB1-CRBN\uff08CRL4CRBN\uff09E3\u6cdb\u7d20\u8fde\u63a5\u9176\u7684\u6d3b\u6027\uff0c\u4f7f\u5305\u62ecIKZF1\u3001IKZF3\u548cCK1\u03b1\u5728\u5185\u7684\u65b0\u57fa\u8d28\u88ab\u62db\u52df\u548c\u6cdb\u7d20\u5316\uff0c\u4ece\u800c\u5bfc\u81f4\u5176\u86cb\u767d\u9176\u4f53\u964d\u89e3\u3002\u5176\u4ed6\u5c0f\u5206\u5b50\uff0c\u5982\u5f02\u6e90\u53cc\u529f\u80fd\u964d\u89e3\u5242\uff08\u4e5f\u79f0\u4e3a\u86cb\u767d\u6c34\u89e3\u9776\u5411\u5d4c\u5408\u4f53\uff1bPROTACs\uff09\uff0c\u5df2\u88ab\u5f00\u53d1\u7528\u4e8e\u964d\u89e3\u5e7f\u6cdb\u7684\u4e34\u5e8a\u76f8\u5173\u9776\u70b9\uff0c\u5305\u62ec\u6fc0\u9176\u3001\u6838\u53d7\u4f53\u548c\u8868\u89c2\u9057\u4f20\u9176\u3002\u8fd9\u4e9b\u5c0f\u5206\u5b50\u964d\u89e3\u5242\u53ef\u540c\u65f6\u4e0eE3\u8fde\u63a5\u9176\u548c\u9776\u86cb\u767d\u7ed3\u5408\uff0c\u4fc3\u8fdb\u5e95\u7269-\u836f\u7269-\u8fde\u63a5\u9176\u4e09\u5143\u590d\u5408\u7269\u7684\u5f62\u6210\u3002\u867d\u7136\u964d\u89e3\u5242\u53ef\u4ee5\u663e\u793a\u51fa\u663e\u8457\u7684\u529f\u6548\u548c\u5bf9\u9776\u6807\u7684\u6301\u7eed\u6d88\u8017\uff0c\u4f46\u6709\u76f8\u5f53\u4e00\u90e8\u5206\u86cb\u767d\u8d28\u5bf9\u8fd9\u79cd\u65b9\u6cd5\u6709\u8f83\u5f3a\u62b5\u6297\u529b\u3002\u81f4\u764c\u8f6c\u5f55\u56e0\u5b50B\u7ec6\u80de\u6dcb\u5df4\u76246\uff08BCL6\uff09\u5c31\u662f\u4e00\u4e2a\u8fd9\u6837\u7684\u4f8b\u5b50\uff0c\u5f02\u6e90\u53cc\u529f\u80fd\u964d\u89e3\u5242\u5bf9\u9776\u86cb\u767d\u7684\u8c03\u8282\u4e0d\u8db3\u4ee5\u8bf1\u5bfc\u751f\u957f\u6291\u5236\u3002<\/p>\n<p><strong>\u3010\u6210\u679c\u7b80\u4ecb\u3011<\/strong><\/p>\n<p>\u8fd1\u65e5\uff0c<strong>\u9ebb\u7701\u7406\u5de5\u5b66\u9662<\/strong><strong>&#8211;<\/strong><strong>\u54c8\u4f5b\u5927\u5b66\u5e03\u7f57\u5fb7\u7814\u7a76\u6240<\/strong><strong>Benjamin L. Ebert<\/strong><strong>\u6559\u6388\u4ee5\u53ca\u6ce2\u58eb\u987f\u8fbe\u7eb3<\/strong><strong>&#8211;<\/strong><strong>\u6cd5\u4f2f\u764c\u75c7\u7814\u7a76\u6240<\/strong><strong>Eric S. Fische<\/strong><strong>\u6559\u6388<\/strong>\u8054\u5408\u62a5\u9053\u4e86\u4e00\u79cd\u9776\u5411\u86cb\u767d\u8d28\u964d\u89e3\u7684\u66ff\u4ee3\u673a\u5236\uff0c\u5728\u8fd9\u79cd\u673a\u5236\u4e2d\uff0c\u5c0f\u5206\u5b50\u8bf1\u5bfc\u9776\u86cb\u767d\u9ad8\u5ea6\u7279\u5f02\u3001\u53ef\u9006\u805a\u5408\uff0c\u7136\u540e\u5c06\u5176\u5c01\u5b58\u5728\u7ec6\u80de\u5185\u5e76\u968f\u540e\u964d\u89e3\u3002BI-3802\u662f\u4e00\u79cd\u5c0f\u5206\u5b50\uff0c\u5b83\u4e0eBCL6\u7684\u5e7f\u6cdb\u590d\u5408\u7269Tramtrack\u548cBric-brac\uff08BTB\uff09\u7ed3\u6784\u57df\u7ed3\u5408\uff0c\u5bfc\u81f4BCL6\u7684\u86cb\u767d\u9176\u4f53\u964d\u89e3\u3002\u901a\u8fc7\u4f7f\u7528\u4f4e\u6e29\u7535\u5b50\u663e\u5fae\u955c\u63ed\u793a\u4e86BCL6\u7ed3\u5408\u5206\u5b50\u7684\u6eb6\u5242\u66b4\u9732\u90e8\u5206\u662f\u5982\u4f55\u5f62\u6210\u590d\u5408\u914d\u4f53-\u86cb\u767d\u8d28\u8868\u9762\u7684\uff0c\u86cb\u767d\u8d28\u8868\u9762\u4e0eBCL6\u540c\u4e8c\u805a\u4f53\u7ed3\u5408\u5f62\u6210\u8d85\u5206\u5b50\u7ed3\u6784\u3002\u836f\u7269\u8bf1\u5bfc\u7684BCL6\u4e1d\u7684\u5f62\u6210\u4fc3\u8fdb\u4e86SIAH1 E3\u6cdb\u7d20\u8fde\u63a5\u9176\u7684\u6cdb\u7d20\u5316\u3002\u7814\u7a76\u7ed3\u679c\u8868\u660e\uff0c\u4e0e\u5176\u4ed6BCL6\u6291\u5236\u5242\u76f8\u6bd4\uff0cBI-3802\u8fd9\u6837\u7684\u5c0f\u5206\u5b50\u53ef\u4ee5\u5c06\u8bf1\u5bfc\u805a\u5408\u548c\u9ad8\u5ea6\u7279\u5f02\u6027\u7684\u86cb\u767d\u8d28\u964d\u89e3\u76f8\u7ed3\u5408\uff0c\u4ece\u800c\u63d0\u9ad8BCL6\u7684\u836f\u7406\u6d3b\u6027\u3002\u8fd9\u4e9b\u53d1\u73b0\u4e3a\u5f00\u53d1\u6cbb\u7597\u836f\u7269\u548c\u5408\u6210\u751f\u7269\u5b66\u5f00\u8f9f\u4e86\u65b0\u7684\u9014\u5f84\u3002\u8be5\u6587\u7ae0\u8fd1\u65e5\u4ee5\u9898\u4e3a\u201c<strong>Small-molecule-induced polymerization triggers degradation of BCL6<\/strong>\u201d\u53d1\u8868\u5728\u77e5\u540d\u671f\u520a<strong>Nature<\/strong>\u4e0a\u3002<\/p>\n<p><strong>\u3010\u56fe\u6587\u5bfc\u8bfb\u3011<\/strong><\/p>\n<p><strong>\u56fe\u4e00\u3001<\/strong><strong>BI-3802<\/strong><strong>\u7684\u5904\u7406\u8bf1\u5bfc<\/strong><strong>BCL6<\/strong><strong>\u7ec6\u80de\u7076\u7684\u53ef\u9006\u5f62\u6210<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-213281\" src=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/1-19.jpg\" alt=\"\" width=\"600\" height=\"315\" srcset=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/1-19.jpg 600w, http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/1-19-300x158.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p><strong>\u56fe\u4e8c\u3001<\/strong><strong>BI-3802<\/strong><strong>\u5728\u4f53\u5916\u8bf1\u5bfc<\/strong><strong>BCL6<\/strong><strong>\u4e1d\u7684\u5f62\u6210<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-213282\" src=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/2-18.jpg\" alt=\"\" width=\"600\" height=\"695\" srcset=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/2-18.jpg 600w, http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/2-18-259x300.jpg 259w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p><strong>\u56fe\u4e09\u3001<\/strong><strong>BCL6<\/strong><strong>\u805a\u5408\u53ef\u589e\u5f3a<\/strong><strong>SIAH1<\/strong><strong>\u7684\u76f8\u4e92\u4f5c\u7528\u548c\u6cdb\u7d20\u5316<\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-213283\" src=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/3-19.jpg\" alt=\"\" width=\"600\" height=\"271\" srcset=\"http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/3-19.jpg 600w, http:\/\/www.cailiaoniu.com\/wp-content\/uploads\/2020\/11\/3-19-300x136.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p>\u6587\u732e\u94fe\u63a5\uff1a<a href=\"https:\/\/www.nature.com\/articles\/s41586-020-2925-1\" target=\"_blank\" rel=\"noopener\">Small-molecule-induced polymerization triggers degradation of BCL6<\/a> (<em>Nature<\/em>, <strong>2020<\/strong>, doi: 10.1038\/s41586-020-2925-1)<\/p>\n<p>\u672c\u6587\u7531\u5927\u5175\u54e5\u4f9b\u7a3f\u3002<\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u3010\u7814\u7a76\u80cc\u666f\u3011 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