{"id":9742,"date":"2024-10-22T13:39:00","date_gmt":"2024-10-22T05:39:00","guid":{"rendered":"https:\/\/sklmo.tsinghua.edu.cn\/?p=9742"},"modified":"2024-10-22T13:39:01","modified_gmt":"2024-10-22T05:39:01","slug":"%e5%88%98%e4%b8%87%e9%87%8c-%e9%a5%b6%e7%87%8f-%e4%b8%81%e5%ae%81%e8%81%94%e5%90%88%e6%94%bb%e5%85%b3btk-protac%e9%99%8d%e8%a7%a3%e5%89%82%e5%af%b9%e8%87%aa%e8%ba%ab%e5%85%8d%e7%96%ab%e7%97%85","status":"publish","type":"post","link":"https:\/\/sklmo.tsinghua.edu.cn\/?p=9742","title":{"rendered":"\u5218\u4e07\u91cc\/\u9976\u71cf\/\u4e01\u5b81\u8054\u5408\u653b\u5173BTK-PROTAC\u964d\u89e3\u5242\u5bf9\u81ea\u8eab\u514d\u75ab\u75c5\u7684\u7f13\u89e3\u4f5c\u7528\u548c\u5206\u5b50\u673a\u5236"},"content":{"rendered":"\n<p>\u5218\u4e07\u91cc\/\u9976\u71cf\/\u4e01\u5b81\u8054\u5408\u653b\u5173BTK-PROTAC\u964d\u89e3\u5242\u5bf9\u81ea\u8eab\u514d\u75ab\u75c5\u7684\u7f13\u89e3\u4f5c\u7528\u548c\u5206\u5b50\u673a\u5236<\/p>\n\n\n\n<p>2024\u5e748\u67086\u65e5\uff0c\u751f\u547d\u4e2d\u5fc3\u5218\u4e07\u91cc\u56e2\u961f\uff0c\u8054\u5408\u6e05\u534e\u5927\u5b66\u836f\u5b66\u9662\u3001\u5206\u5b50\u80bf\u7624\u5b66\u5168\u56fd\u91cd\u70b9\u5b9e\u9a8c\u5ba4\uff08\u6e05\u534e\uff09\u9976\u71cf\u56e2\u961f\u548c\u5317\u4eac\u5927\u5b66\u80bf\u7624\u533b\u9662\u4e01\u5b81\u56e2\u961f\u643a\u624b\u5728Cell 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&nbsp; &nbsp; 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src=\"https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/image-2.png\" alt=\"\" class=\"wp-image-9744\" srcset=\"https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/image-2.png 557w, https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/image-2-300x100.png 300w\" sizes=\"(max-width: 557px) 100vw, 557px\" \/><figcaption class=\"wp-element-caption\">\u56fe1 L18I\u53ef\u6709\u6548\u7f13\u89e3BM12\u8bf1\u5bfc\u7684\u5c0f\u9f20\u72fc\u75ae\u75c7\u72b6<\/figcaption><\/figure><\/div>\n\n\n<p>\u00a0\u9664B\u7ec6\u80de\u5916\uff0cBTK\u5728\u9ad3\u7cfb\u7ec6\u80de\u5927\u91cf\u8868\u8fbe\uff0c\u5982\u5355\u6838\/\u5de8\u566c\u7ec6\u80de\u3001\u4e2d\u6027\u7c92\u7ec6\u80de\u548c\u6811\u7a81\u72b6\u7ec6\u80de\u7b49\u3002\u5728DAH\u4e2d\uff0cB\u7ec6\u80de\u548c\u9ad3\u7cfb\u6765\u6e90\u7684\u5355\u6838\/\u5de8\u566c\u7ec6\u80de\u88ab\u8ba4\u4e3a\u5728\u75be\u75c5\u8fdb\u5c55\u4e2d\u53d1\u6325\u81f3\u5173\u91cd\u8981\u7684\u4f5c\u7528\uff0c\u800cBTK\u901a\u8fc7\u8c03\u8282TLR\u4fe1\u53f7\u3001Fc\u03b3R\u4fe1\u53f7\u548cNLRP3\u708e\u6027\u5c0f\u4f53\u53c2\u4e0e\u9ad3\u7cfb\u7ec6\u80de\u7684\u6d3b\u5316\u548c\u529f\u80fd\uff0c\u56e0\u6b64BTK\u964d\u89e3\u5242\u53ef\u80fd\u5728DAH\u4e2d\u53d1\u6325\u591a\u65b9\u9762\u7684\u4f5c\u7528\u3002\u8be5\u8bba\u6587\u7ed3\u679c\u663e\u793a\uff0cBTK\u964d\u89e3\u5242L18I\u53ef\u4ee5\u663e\u8457\u964d\u4f4eDAH\u60a3\u75c5\u7387\uff0c\u7f13\u89e3\u80ba\u51fa\u8840\u548c\u514d\u75ab\u7ec6\u80de\u6d78\u6da6\uff0c\u51cf\u5c11\u5c0f\u9f20\u6b7b\u4ea1\u7387\uff08\u56fe2\uff09\u3002\u540c\u65f6\u80ba\u90e8\u7ec6\u80de\u6d41\u5f0f\u7ed3\u679c\u663e\u793aL18I\u7ed9\u836f\u6709\u52a9\u4e8e\u80ba\u90e8\u6b63\u5e38\u514d\u75ab\u7ec6\u80de\u5fae\u73af\u5883\u7684\u7ef4\u6301\uff0c\u5305\u62ec\u51cf\u5c11Ly6Chigh\u548cLy6Clow\u5355\u6838\u7ec6\u80de\u7684\u6d78\u6da6\u3002\u7ec6\u80de\u5185BTK\u542b\u91cf\u68c0\u6d4b\u8868\u660eL18I\u4e3b\u8981\u901a\u8fc7\u4f5c\u7528\u4e8e\u5355\u6838\u7ec6\u80de\u7f13\u89e3DAH\u75c7\u72b6\uff0c\u5176\u6b21\u662fB\u7ec6\u80de\u3001\u6811\u7a81\u72b6\u7ec6\u80de\u3001\u5de8\u566c\u7ec6\u80de\u548c\u4e2d\u6027\u7c92\u7ec6\u80de\u3002\u5728\u7f13\u89e3\u5c0f\u9f20DAH\u8868\u578b\u5305\u62ec\u80ba\u90e8\u51fa\u8840\u3001\u708e\u75c7\u4ee5\u53ca\u7ec6\u80de\u6d78\u6da6\u7b49\u65b9\u9762\uff0cBTK\u964d\u89e3\u5242L18I\u90fd\u8981\u4f18\u4e8e\u6291\u5236\u5242Ibrutinib\u3002\u6b64\u5916\u4f53\u5916\u5b9e\u9a8c\u4e5f\u8868\u660e\uff0cL18I\u53ef\u4ee5\u6709\u6548\u964d\u4f4e\u5355\u6838\/\u5de8\u566c\u7ec6\u80de\u523a\u6fc0\u6d3b\u5316\u540e\u708e\u6027\u7ec6\u80de\u56e0\u5b50\u7684\u8868\u8fbe\u548c\u5206\u6ccc\u3002<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"554\" height=\"285\" src=\"https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/ca37b12ace1707d8f2adc833b3216fe9.png\" alt=\"\" class=\"wp-image-9745\" srcset=\"https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/ca37b12ace1707d8f2adc833b3216fe9.png 554w, https:\/\/sklmo.tsinghua.edu.cn\/wp-content\/uploads\/2024\/10\/ca37b12ace1707d8f2adc833b3216fe9-300x154.png 300w\" sizes=\"(max-width: 554px) 100vw, 554px\" \/><figcaption class=\"wp-element-caption\">\u56fe2 L18I\u53ef\u6709\u6548\u7f13\u89e3pristane\u8bf1\u5bfc\u7684\u5c0f\u9f20\u72fc\u75ae\u548c\u5f25\u6f2b\u6027\u80ba\u51fa\u8840\u75c7\u72b6<\/figcaption><\/figure><\/div>\n\n\n<p>\u7efc\u5408\u4e0a\u8ff0\u7ed3\u679c\uff0cL18I\u4e0d\u4ec5\u53ef\u4ee5\u901a\u8fc7\u51cf\u5c11\u6297\u4f53\u5206\u6ccc\u6709\u6548\u7f13\u89e3\u72fc\u75ae\u75c7\u72b6\uff0c\u8fd8\u53ef\u4ee5\u901a\u8fc7\u51cf\u8f7b\u708e\u75c7\u53cd\u5e94\u6765\u7f13\u89e3DAH\u3002\u8003\u8651\u5230Ibrutinib\u7531\u4e8e\u8131\u9776\u6548\u5e94\u548c\u5bfc\u81f4\u65b0\u7a81\u53d8\u7684\u51fa\u73b0\u800c\u4ea7\u751f\u7684\u591a\u91cd\u526f\u4f5c\u7528\uff0cL18I\u6709\u53ef\u80fd\u6210\u4e3a\u4e00\u79cd\u66f4\u5b89\u5168\u3001\u66f4\u6709\u6548\u7684\u66ff\u4ee3BTK\u6291\u5236\u5242\u6cbb\u7597\u81ea\u8eab\u514d\u75ab\u6027\u75be\u75c5\u7684\u65b9\u6848\u3002\u6b64\u5916\uff0c\u8be5\u8bba\u6587\u8fd8\u5f3a\u8c03\u4e86L18I\u5728\u6291\u5236TLR\u4fe1\u53f7\u901a\u8def\u6fc0\u6d3b\u65b9\u9762\u76f8\u6bd4\u4e8eIbrutinib\u7684\u4f18\u52bf\uff0c\u4e5f\u5c55\u793a\u51faL18I\u5728\u5355\u6838\u7ec6\u80de\u4e3b\u5bfc\u7684\u75be\u75c5\u4e2d\u7684\u4f18\u8d8a\u8868\u73b0\uff0c\u56e0\u6b64L18I\u53ef\u80fd\u5728TLR\u4fe1\u53f7\u8fc7\u5ea6\u6d3b\u5316\u4ee5\u53ca\u9ad3\u7cfb\u7ec6\u80de\u4e3b\u5bfc\u7684\u75be\u75c5\u4e2d\u53d1\u6325\u66f4\u591a\u7684\u4f5c\u7528\u3002<\/p>\n\n\n\n<p>&nbsp; &nbsp; &nbsp;\u751f\u547d\u4e2d\u5fc3PI\u5218\u4e07\u91cc\u662f\u8bba\u6587\u7684\u6700\u540e\u901a\u8baf\u4f5c\u8005\uff08Lead Corresponding author\uff09\uff0c\u6e05\u534e\u5927\u5b66\u836f\u5b66\u9662\u3001\u5206\u5b50\u80bf\u7624\u5b66\u5168\u56fd\u91cd\u70b9\u5b9e\u9a8c\u5ba4\uff08\u6e05\u534e\uff09\u9976\u71cf\u6559\u6388\u548c\u5317\u4eac\u5927\u5b66\u80bf\u7624\u533b\u9662\u4e01\u5b81\u7814\u7a76\u5458\u662f\u672c\u6587\u7684\u5171\u540c\u901a\u8baf\u4f5c\u8005\uff08co-corresponding author\uff09\u3002\u751f\u547d\u4e2d\u5fc3\u5218\u4e07\u91cc\u56e2\u961f\u5df2\u6bd5\u4e1a\u6731\u74a8\u535a\u58eb\u3001\u836f\u5b66\u9662\u9976\u71cf\u56e2\u961f\u5df2\u6bd5\u4e1a\u6768\u5b50\u9ed8\u535a\u58eb\u3001\u5317\u4eac\u5927\u5b66\u80bf\u7624\u533b\u9662\u4e01\u5b81\u56e2\u961f\u7684\u674e\u632f\u519b\u8001\u5e08\uff1b\u6e05\u534e\u5927\u5b66\u5728\u8bfb\u535a\u58eb\u751f\u5f20\u96e8\u7b71\u548c\u674e\u5e7f\u6668\u4e3a\u8be5\u8bba\u6587\u5171\u540c\u7b2c\u4e00\u4f5c\u8005\u3002\u8be5\u7814\u7a76\u5f97\u5230\u56fd\u5bb6\u81ea\u7136\u79d1\u5b66\u57fa\u91d1\u59d4\u91cd\u5927\u7814\u7a76\u8ba1\u5212\u3001\u4e13\u9879\u9879\u76ee\uff0c\u56fd\u5bb6\u79d1\u6280\u90e8\u91cd\u70b9\u7814\u53d1\u8ba1\u5212\u3001\u5317\u4eac\u5e02\u81ea\u7136\u79d1\u5b66\u57fa\u91d1\u91cd\u70b9\u9879\u76ee\u3001\u6e05\u534e\u5927\u5b66\u6625\u98ce\u57fa\u91d1\u3001\u751f\u547d\u79d1\u5b66\u8054\u5408\u4e2d\u5fc3\u3001\u6e05\u534e\u5927\u5b66\u514d\u75ab\u5b66\u7814\u7a76\u6240\u3001\u6e05\u534e\u5927\u5b66\u4e07\u79d1\u516c\u5171\u536b\u751f\u5b66\u9662\u548c\u5317\u4eac\u5927\u5b66\u80bf\u7624\u533b\u9662\u7684\u7814\u7a76\u57fa\u91d1\u8d44\u52a9\u3002<\/p>\n\n\n\n<p>&nbsp; &nbsp; &nbsp;BTK-PROTAC\u964d\u89e3\u5242\u5408\u4f5c\u5f00\u53d1\u5e7f\u544a\uff08\u77ed\u671f\u6709\u6548\uff09\uff1a\u6e05\u534e\u5927\u5b66\u5218\u4e07\u91cc\u548c\u9976\u71cf\u56e2\u961f\u5177\u5907BTK-PROTAC\u964d\u89e3\u5242L18I\u7684\u77e5\u8bc6\u4ea7\u6743\u548cPre-clinical\u7814\u7a76\u4f53\u7cfb\uff0c\u6b22\u8fce\u5bf9\u6b64\u5f00\u5c55\u76f8\u5173\u80bf\u7624\u548c\u81ea\u8eab\u514d\u75ab\u75be\u75c5\u7684\u540e\u671f\u5f00\u53d1\u5408\u4f5c\uff08Email: liulab@mail.tsinghua.edu.cn\uff09\u3002<\/p>\n\n\n\n<p>&nbsp; &nbsp; &nbsp; &nbsp;\u535a\u58eb\u540e\u548c\u7814\u7a76\u52a9\u7406\u62db\u8058\u5e7f\u544a\uff08\u957f\u671f\u6709\u6548\uff09\uff1a\u5218\u4e07\u91cc\u56e2\u961f\u81f4\u529b\u4e8eB\u7ec6\u80de\u6297\u539f\u53d7\u4f53\u4ecb\u5bfc\u7684\u514d\u75ab\u8bc6\u522b\u3001\u514d\u75ab\u6d3b\u5316\u3001\u6297\u4f53\u5e94\u7b54\u53ca\u76f8\u5173\u75be\u75c5\u7684\u7814\u7a76\uff0c\u5728\u56fd\u5185\u5916\u4e3b\u6d41\u7684\u751f\u7269\u533b\u5b66\u671f\u520a\u5171\u8ba1\u53d1\u8868SCIE\u6536\u5f55\u7684\u7814\u7a76\u8bba\u6587\u767e\u4f59\u7bc7\uff081\u7bc7Science\u30011\u7bc7Cell\u30011\u7bc7Science Immunology\u30011\u7bc7Nature Immunology\u30011\u7bc7Immunity\u30011\u7bc7PNAS\u30011\u7bc7J Clin Invest\u30013\u7bc7J Exp Med\u30011\u7bc7Ann Rheum Dis\u30012\u7bc7Cell Research\u30012\u7bc7Protein Cell\u30014\u7bc7Nature Communications\u30011\u7bc7Science Advances\u30011\u7bc7PLoS Biology\u30011\u7bc7Science Signaling\u30011\u7bc7J Cell Biol\u30011\u7bc7J Allergy Clin Immunol\u30012\u7bc7Leukemia\u30014\u7bc7J 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