{"id":2260,"date":"2026-10-23T17:54:31","date_gmt":"2026-10-23T09:54:31","guid":{"rendered":"https:\/\/www.millibuff.com\/?p=2260"},"modified":"2026-10-23T17:55:16","modified_gmt":"2026-10-23T09:55:16","slug":"%e5%b0%8f%e7%89%9b%e6%b4%9e%e5%af%9f-%e4%b8%a4%e5%91%a8%e7%a0%b8%e4%b8%8b13-7%e4%ba%bf%e7%be%8e%e5%85%83%ef%bc%9a%e8%be%89%e7%91%9e%e5%92%8c%e7%a4%bc%e6%9d%a5%e5%90%8c%e6%97%b6%e5%9c%a8%e6%8a%a2","status":"publish","type":"post","link":"https:\/\/www.millibuff.com\/?p=2260","title":{"rendered":"\u5c0f\u725b\u6d1e\u5bdf| \u4e24\u5468\u7838\u4e0b13.7\u4ebf\u7f8e\u5143\uff1a\u8f89\u745e\u548c\u793c\u6765\u540c\u65f6\u5728\u62a2\u7684\u8fd9\u6761”\u901a\u9053”\uff0c\u5230\u5e95\u662f\u4ec0\u4e48\uff1f"},"content":{"rendered":"\n

2026\u5e7410\u6708\uff0c\u4e24\u5468\u4e4b\u5185\uff0c\u4e00\u4e2a\u6b64\u524d\u51e0\u4e4e\u65e0\u4eba\u95ee\u6d25\u7684\u9776\u70b9\u51fa\u73b0\u4e86\u4e24\u7b14\u5927\u989d\u4ea4\u6613\u3002<\/strong>10\u670813\u65e5\uff0c\u8f89\u745e\u4e0e\u5df4\u9ece\u751f\u7269\u6280\u672f\u516c\u53f8Enodia\u7b7e\u7f72\u7814\u7a76\u5408\u4f5c\u4e0e\u8bb8\u53ef\u534f\u8bae\uff0c\u6f5c\u5728\u603b\u989d\u8d85\u8fc75\u4ebf\u7f8e\u5143[1,2]\uff1b\u4ec5\u4e00\u5468\u524d\uff0c\u793c\u6765\u5411Gate Bioscience\u8ffd\u52a08.7\u4ebf\u7f8e\u5143[3,4]\u3002\u4e24\u5468\u5185\u65b0\u589e\u7684\u6f5c\u5728\u4ea4\u6613\u989d\u5408\u8ba1\u7ea613.7\u4ebf\u7f8e\u5143\uff1b\u82e5\u8ba1\u5165\u793c\u67652025\u5e74\u4e0eGate\u8fbe\u6210\u7684\u9996\u7b148.56\u4ebf\u7f8e\u5143\u534f\u8bae\uff0c\u793c\u6765\u4e00\u5bb6\u5728\u8fd9\u6761\u901a\u9053\u4e0a\u7684\u7d2f\u8ba1\u627f\u8bfa\u5df2\u8fbe\u7ea617\u4ebf\u7f8e\u5143[3,4]\u3002\u800c\u652f\u6491\u8fd9\u4e24\u7b14\u4ea4\u6613\u7684\uff0c\u662f\u8fd9\u6837\u4e00\u4e2a\u4e8b\u5b9e\uff1a\u5168\u7403\u8fc4\u4eca\u53ea\u6709\u4e00\u6b3eSec61\u6291\u5236\u5242\u8fdb\u5165\u8fc7\u4e34\u5e8a\uff0c\u800c\u4e14\u5df2\u7ecf\u505c\u6b62\u5165\u7ec4\uff0c\u6ca1\u6709\u89c2\u5bdf\u5230\u4efb\u4f55\u5ba2\u89c2\u7f13\u89e3[5,6]\u3002<\/strong><\/p>\n\n\n\n

<\/p>\n\n\n\n

\u4e00\u3001\u4e0d\u662f<\/strong>“<\/strong>\u964d\u89e3<\/strong>“<\/strong>\uff0c\u662f<\/strong>“<\/strong>\u62e6\u622a<\/strong>“<\/strong><\/h5>\n\n\n\n

\u8981\u7406\u89e3Sec61\u4e3a\u4ec0\u4e48\u503c\u94b1\uff0c\u5f97\u5148\u770b\u6e05\u695a\u9776\u5411\u86cb\u767d\u964d\u89e3\uff08TPD\uff09\u73b0\u5728\u7684\u7248\u56fe\u3002PROTAC\u548c\u5206\u5b50\u80f6\u5229\u7528E3\u6cdb\u7d20\u8fde\u63a5\u9176\u7cfb\u7edf\uff0c\u6807\u8bb0\u5df2\u7ecf\u6298\u53e0\u6210\u719f\u7684\u80de\u5185\u86cb\u767d\uff0c\u9001\u53bb\u86cb\u767d\u9176\u4f53\u964d\u89e3\uff1bLYTAC\u901a\u8fc7\u7ec6\u80de\u8868\u9762\u53d7\u4f53\uff0c\u628a\u819c\u86cb\u767d\u548c\u5206\u6ccc\u86cb\u767d\u62d6\u8fdb\u6eb6\u9176\u4f53\u3002\u8fd9\u4e24\u6761\u8def\u7ebf\u7684\u5171\u540c\u70b9\u662f\uff0c\u5b83\u4eec\u90fd\u4f5c\u7528\u5728\u86cb\u767d\u751f\u547d\u5468\u671f\u7684”\u672b\u7aef”\uff1a\u86cb\u767d\u5df2\u7ecf\u9020\u597d\u4e86\uff0c\u518d\u60f3\u529e\u6cd5\u6e05\u6389\u3002<\/p>\n\n\n\n

Sec61\u6291\u5236\u5242\u8d70\u7684\u662f\u53e6\u4e00\u6761\u8def\u3002Sec61\u662f\u5185\u8d28\u7f51\u819c\u4e0a\u7684\u86cb\u767d\u8f6c\u8fd0\u901a\u9053\uff0c\u8d1f\u8d23\u628a\u65b0\u5408\u6210\u7684\u5206\u6ccc\u578b\u86cb\u767d\u548c\u8de8\u819c\u86cb\u767d\u9001\u8fdb\u5185\u8d28\u7f51[7]\u3002Itskanov\u7b49\u6307\u51fa\uff0cSec61\u590d\u5408\u7269”plays essential roles in biosynthesis of more than one-third of proteins in all species”[8]\uff1bRehan\u7b49\u5219\u5199\u4e3a\u8fd9\u7c7b\u86cb\u767d”comprise approximately one-third of the eukaryotic proteome”[9]\u3002Sec61\u6291\u5236\u5242\u7684\u4f5c\u7528\u65b9\u5f0f\u662f\u5728\u86cb\u767d\u5408\u6210\u4f4d\u70b9\u76f4\u63a5\u62e6\u622a\uff1a\u9009\u62e9\u6027\u8c03\u8282Sec61\u901a\u9053\uff0c\u963b\u6b62\u81f4\u75c5\u86cb\u767d\u8fdb\u5165\u5206\u6ccc\u9014\u5f84\uff0c\u4f7f\u5176\u88ab\u91cd\u65b0\u5bfc\u5411\u80de\u8d28\u86cb\u767d\u9176\u4f53\u964d\u89e3\u3002Enodia\u5c06\u5176\u5b9a\u4e49\u4e3a”targeted protein degradation at the point of synthesis”[1]\uff1bJ Pharmacol Exp Ther 2025\u5bf9KZR-261\u7c7b\u5316\u5408\u7269\u7684\u63cf\u8ff0\u5219\u662f”a novel mechanism for blocking expression of oncogenic factors”[10]\u3002<\/p>\n\n\n\n

\u8fd9\u4e2a”\u9760\u524d”\u610f\u5473\u7740\uff0cSec61\u7684\u5ba2\u6237\u86cb\u767d\u540d\u5355\u4e0a\u5217\u7740HER3\u3001PD-1\u3001VEGF-A\u3001VEGFR\u3001EGFR\u3001IL-7R\u3001TNF-\u03b1\u7b49\u2014\u2014JPET 2025\u628a\u8fd9\u7c7b\u5ba2\u6237\u6982\u62ec\u4e3a”\u81f4\u764c\u53d7\u4f53\u3001\u514d\u75ab\u76d1\u89c6\u5206\u5b50\u4e0e\u7ec6\u80de\u56e0\u5b50”\u4e09\u7c7b\uff0c\u51e0\u4e4e\u5168\u662fPROTAC\u4e0d\u5bb9\u6613\u591f\u5230\u7684\u5206\u6ccc\u578b\u548c\u819c\u7ed3\u5408\u578b\u9776\u70b9[10,23]\u3002<\/p>\n\n\n\n

\u4e8c\u3001\u7ed3\u6784\uff1a\u4e03\u4e2a\u5206\u5b50\uff0c\u5171\u7528\u540c\u4e00\u4e2a\u53e3\u888b<\/strong><\/h5>\n\n\n\n

Sec61\u6291\u5236\u5242\u7684\u79d1\u5b66\u6027\uff0c\u57282023\u5e74\u88ab\u4e24\u7bc7\u80cc\u9760\u80cc\u7684Nature Chemical Biology\u8bba\u6587\u5750\u5b9e\u3002<\/p>\n\n\n\n

Itskanov\u7b49\u4ee5\u8fd1\u539f\u5b50\u5206\u8fa8\u7387\u89e3\u6790\u4e86\u4eba\u7c7bSec61\u4e0e\u4e03\u79cd\u7ed3\u6784\u8fe5\u5f02\u7684\u5c0f\u5206\u5b50\u6291\u5236\u5242\u7684\u590d\u5408\u7269\u7ed3\u6784\u2014\u2014cotransin\u3001decatransin\u3001apratoxin\u3001ipomoeassin\u3001mycolactone\u3001cyclotriazadisulfonamide\u548ceeyarestatin\u3002\u7ed3\u8bba\u975e\u5e38\u5e72\u51c0\uff1a<\/p>\n\n\n\n

All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening.<\/p>\n\n\n\n

\u4e03\u79cd\u5316\u5b66\u7ed3\u6784\u6beb\u65e0\u76f8\u4f3c\u4e4b\u5904\u7684\u5206\u5b50\uff0c\u6324\u5728\u540c\u4e00\u4e2a\u53e3\u888b\u91cc\uff0c\u6297\u6027\u7a81\u53d8\u5168\u90e8\u805a\u96c6\u4e8e\u6b64[8]\u3002\u8fd9\u662f”\u5728\u9776”\u6700\u786c\u7684\u8bc1\u636e\u3002<\/p>\n\n\n\n

\u540c\u671fRehan\u7b49\u805a\u7126\u7684KZR-8445\u5219\u662f\u53e6\u4e00\u79cd\u673a\u5236\u65b9\u5411\uff1a\u5b83”occupies the fully opened Sec61 lateral gate and blocks access to the lumenal plug domain”\uff0c\u5e76\u4e14”traps select signal peptides in the Sec61 channel”[9]\u3002\u4e24\u7bc7\u8bba\u6587\u63cf\u8ff0\u7684\u6784\u8c61\u666f\u89c2\u5e76\u4e0d\u76f8\u540c\u2014\u2014\u4e00\u4e2a\u7a33\u5b9aplug\u4e8e\u95ed\u5408\u6001\uff0c\u4e00\u4e2a\u5360\u636e\u5b8c\u5168\u5f00\u653e\u7684\u4fa7\u95e8\u2014\u2014\u8fd9\u6070\u6070\u8bf4\u660e\uff0cSec61\u6291\u5236\u7684\u673a\u5236\u6bd4”\u5835\u4f4f\u901a\u9053”\u8981\u590d\u6742[8,9]\u3002<\/p>\n\n\n\n

Coibamide<\/strong> A<\/strong>\uff08<\/strong>CbA<\/strong>\uff09\u4e0e\u4e2d\u56fd\u56e2\u961f\u7684\u5de5\u4f5c<\/strong><\/h6>\n\n\n\n

2026\u5e74Cell Chemical Biology\u7684\u7814\u7a76\u4ee53.1 \u00c5\u5206\u8fa8\u7387\u89e3\u6790\u4e86CbA\u4e0e\u4eba\u7c7bSec61\u7684\u590d\u5408\u7269\u7ed3\u6784\uff08PDB 9YWS\uff09\uff0c\u53d1\u73b0CbA\u91c7\u7528\u72ec\u7279\u7684”\u5957\u7d22\u6837”\u6784\u8c61\u5360\u636e\u4fa7\u95e8\uff0c\u76f8\u4e92\u4f5c\u7528\u6bd4\u540c\u7c7b\u6291\u5236\u5242”particularly more expansive”[11]\u3002\u57fa\u4e8e\u8fd9\u4e00\u7ed3\u6784\uff0c\u7814\u7a76\u8005\u5f00\u53d1\u4e86\u9aa8\u67b6\u5c01\u7aef\u578b\uff08backbone-caging\uff09\u524d\u836f\u7b56\u7565\uff0c\u901a\u8fc7”controlled perturbation of intramolecular and protein hydrogen bonding interactions”\u53ef\u9006\u5c4f\u853d\u6d3b\u6027\uff0c\u5176\u4e2d\u7f3a\u6c27\u6fc0\u6d3b\u7248\u672c\u5728\u4f53\u5185\u5c55\u793a\u4e86\u6539\u5584\u7684\u6cbb\u7597\u6307\u6570[11]\u3002\u540c\u671f\u8fd8\u5728J Med Chem\u53d1\u8868\u4e86CbA\u7c7b\u4f3c\u7269\u4f5c\u4e3a\u8f7d\u8377\u7684\u6297EGFR ADC\u5de5\u4f5c[12]\u3002<\/p>\n\n\n\n

\u9009\u62e9\u6027\u4ece\u54ea<\/strong>\u91cc\u6765\uff1f\u7b54\u6848\u5728\u4fe1\u53f7\u80bd<\/strong><\/h6>\n\n\n\n

2024\u5e74Nature Chemical Biology\u7684Wenzell\u7b49\u5efa\u7acb\u4e86\u4e00\u4e2a\u57fa\u4e8e\u8367\u5149\u62a5\u544a\u7cfb\u7edf\u7684\u6c60\u5316\u7ec6\u80de\u7b5b\u9009\u5e73\u53f0\uff0c\u53ef\u4ee5\u5e76\u884c\u5206\u6790\u8fd1\u4e4e\u5168\u90e8\u4eba\u7c7b\u4fe1\u53f7\u80bd\u3002\u4ed6\u4eec\u53d1\u73b0\uff1acotransin\u7684\u6291\u5236\u6d3b\u6027\u4f9d\u8d56\u4e8e\u6bcf\u4e2aSec61\u5ba2\u6237\u86cb\u767d\u72ec\u6709\u7684\u4fe1\u53f7\u80bd\uff1b\u901a\u8fc7\u6bd4\u8f83\u5c0f\u9f20\u548c\u4eba\u7c7b\u76f4\u7cfb\u540c\u6e90\u7269\uff0c\u63ed\u793a\u4e86\u7cbe\u6c28\u9178\u5728\u4fe1\u53f7\u80bd\u4e2d\u7684\u4f4d\u7f6e\u4f9d\u8d56\u6027\u6548\u5e94[13]\u3002\u8be5\u6587\u5728HER3\u4fe1\u53f7\u80bd\u4e0a\u9a8c\u8bc1\u4e86\u8fd9\u4e00\u70b9\uff0c\u5e76\u8bc1\u660e\u9009\u62e9\u6027\u66f4\u9ad8\u7684cotransin\u7c7b\u4f3c\u7269KZR-9873\u53ef\u901a\u8fc7HER3\u963b\u65adCAL27\u7ec6\u80de\u589e\u6b96[13]\u3002\u6362\u53e5\u8bdd\u8bf4\uff0c\u9009\u62e9\u6027\u4e0d\u662f\u9760”\u6311\u9776\u70b9”\uff0c\u800c\u662f\u9760”\u6311\u4fe1\u53f7\u80bd”\u2014\u2014\u8fd9\u4e00\u53d1\u73b0\uff0c\u6210\u4e86\u540e\u9762\u6240\u6709\u9009\u62e9\u6027\u5de5\u7a0b\u7684\u5730\u57fa\u3002<\/p>\n\n\n\n

\u4e09\u3001\u4e34\u5e8a\uff1a\u552f\u4e00\u7684\u90a3\u6b3e\u836f\uff0c\u7ed9\u51fa\u4e86\u4ec0\u4e48\u7b54\u6848<\/strong><\/h5>\n\n\n\n

Kezar Life Sciences\u7684KZR-261\u662f\u8fc4\u4eca\u552f\u4e00\u8fdb\u5165\u4e34\u5e8a\u7684Sec61\u6291\u5236\u5242[5,6]\u3002\u5b83\u4e0eKZR-834\u662f\u7531CADA\u9aa8\u67b6\u4f18\u5316\u800c\u6765\u7684\u5e76\u5217\u7ed3\u6784\u7c7b\u4f3c\u7269\u2014\u2014KZR-834\u7528\u4e8e\u4e34\u5e8a\u524d\u8868\u5f81\uff0cKZR-261\u88ab\u63d0\u540d\u8fdb\u5165\u4e34\u5e8a[10]\u3002<\/p>\n\n\n\n

\u9009\u62e9\u6027\u6570\u636e\u9700\u8981\u533a\u5206\u53e3\u5f84<\/strong><\/h6>\n\n\n\n

Kezar\u5728AACR 2021\u516c\u5e03\u7684\u5b9a\u91cf\u86cb\u767d\u8d28\u7ec4\u5b66\u6570\u636e\u663e\u793a\uff0c\u5728\u591a\u79cd\u80bf\u7624\u7ec6\u80de\u7cfb\u7684\u819c\uff0fER\u7ec4\u5206\u4e2d\u5171\u68c0\u51fa2222<\/strong>\u4e2aSec61\u5ba2\u6237\u86cb\u767d\uff0c\u5360\u5df2\u6ce8\u91caSec61\u5ba2\u6237\u7ec4\u768430%\u4ee5\u4e0a\uff0c\u5176\u4e2d\u53ea\u67095%-17%\u88ab\u6291\u5236\u8d85\u8fc750%[14]\u3002\u516c\u53f8\u540c\u671f\u62ab\u9732\u7684\u53e6\u4e00\u7ec4\u6570\u636e\u663e\u793a\uff1a\u5728\u80bf\u7624\u7ec6\u80de\u4e2d\u7ea610%\u7684Sec61\u5ba2\u6237\u86cb\u767d\u8868\u8fbe\u4e0b\u8c03\u81f3\u5c112\u500d\uff0c\u800c\u5728\u975e\u8f6c\u5316\u7ec6\u80de\u4e2d\u4e0d\u8db35%[14]\u30022026\u5e74\u4e00\u7bc7\u7ecf\u540c\u884c\u8bc4\u8bae\u7684SEC61G\u7efc\u8ff0\u7ed9\u51fa\u7684\u53e3\u5f84\u66f4\u4e25\u683c\u2014\u2014KZR-261\u4ec5\u6291\u5236\u7ea62%-5%\u7684Sec61\u5ba2\u6237\u86cb\u767d\uff0c\u4e3b\u8981\u4e3a\u5206\u6ccc\u578b\u4e0eI\uff0fII\u578b\u8de8\u819c\u86cb\u767d[22]\u3002<\/p>\n\n\n\n

\u9700\u8981\u63d0\u9192\u7684\u662f\uff0c\u4e0d\u540c\u53e3\u5f84\u6d4b\u91cf\u5bf9\u8c61\u4e0d\u540c\u3001\u4e0d\u53ef\u76f4\u63a5\u6362\u7b97\uff1aAACR 2021\u7684”5%-17%”\u6765\u81ea\u5b9a\u91cf\u86cb\u767d\u8d28\u7ec4\u5b66\uff0c\u6d4b\u91cf\u7684\u662f\u5ba2\u6237\u86cb\u767d\u8868\u8fbe\u91cf\u7684\u53d8\u5316\u5e45\u5ea6[14]\uff1bJPET 2025\u5efa\u7acb\u7684\u5219\u662fGaussia\u8367\u5149\u7d20\u9176\uff08Gluc\uff09\u6807\u8bb0\u4fe1\u53f7\u80bd\u7684\u62a5\u544a\u57fa\u56e0\u4f53\u7cfb\uff0c\u6d4b\u91cf\u7684\u662f\u4fe1\u53f7\u80bd\u5c42\u9762\u7684\u8f6c\u8fd0\u6291\u5236\u6548\u529b[10]\u3002<\/p>\n\n\n\n

\u771f\u6b63\u7684\u53c2\u7167\u7cfb\u662f\u5929\u7136\u4ea7\u7269\u3002Apratoxin A\u4e0emycolactone\u76f4\u63a5\u7ed3\u5408Sec61\u03b1\uff0c“<\/strong>\u4ee5\u76f8\u8fd1\u6548\u529b\u6291\u5236\u6240\u6709\u88ab\u6d4b\u8bd5\u7684<\/strong>Sec61<\/strong>\u5ba2\u6237\u86cb\u767d\u7684\u5185\u8d28\u7f51\u8f6c\u8fd0<\/strong>“<\/strong>\uff0c\u5373\u7f3a\u4e4f\u5e95\u7269\u9009\u62e9\u6027[10,22]\u3002\u56e0\u6b64\uff0cKZR-261\u7684”\u9009\u62e9\u6027”\u662f\u76f8\u5bf9\u4e8e\u5929\u7136\u4ea7\u7269\u5168\u5c40\u6291\u5236\u5242\u800c\u8a00\u7684\u76f8\u5bf9\u9009\u62e9\u6027\uff0c\u4e0d\u662f\u53ea\u6253\u4e00\u4e2a\u9776\u70b9\u7684\u7edd\u5bf9\u72ed\u7a84\u3002<\/p>\n\n\n\n

\u7597\u6548\uff1a<\/strong>\u96f6\u5ba2\u89c2<\/strong>\u7f13\u89e3<\/strong><\/h6>\n\n\n\n

I\u671f\u4e34\u5e8a\u8bd5\u9a8c\u5165\u7ec461\u540d\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\uff0c\u672a\u89c2\u5bdf\u5230\u4efb\u4f55\u5ba2\u89c2\u7f13\u89e3\u300261\u4f8b\u4e2d\uff0c5\u540d\u60a3\u8005\uff08\u5176\u4e2d2\u4f8b\u9ed1\u8272\u7d20\u7624\uff09\u5728\u5242\u91cf\u9012\u589e\u90e8\u5206\u5b9e\u73b0\u75be\u75c5\u7a33\u5b9a\u22654\u4e2a\u6708\uff0c\u5176\u4e2d2\u4f8b\uff08\u9ed1\u8272\u7d20\u7624\u3001\u5934\u9888\u764c\uff09\u7a33\u5b9a\u226512\u4e2a\u6708[6]\u3002JPET\u6458\u8981\u7684\u539f\u8bdd\u662f”well tolerated at doses that achieved durable stable disease”\u2014\u2014\u8fd9\u53e5\u8bdd\u9a8c\u8bc1\u7684\u662f\u8010\u53d7\u6027\u548c\u9776\u70b9\u5360\u4f4d\uff0c\u4e0d\u662f\u6297\u80bf\u7624\u6d3b\u6027[10]\u3002Kezar\u57282024\u5e748\u6708\u505c\u6b62\u5165\u7ec4\uff0c\u5b98\u65b9\u7406\u7531\u662f\u5c06\u4e34\u5e8a\u8d44\u6e90\u91cd\u65b0\u5206\u914d\u5230\u5176\u4ed6\u9879\u76ee[5,6]\u3002\u628a\u8fd9\u4e00\u5546\u4e1a\u51b3\u7b56\u8bfb\u6210”\u6cbb\u7597\u7a97\u53e3\u672a\u8fbe\u6807”\u53ef\u80fd\u8fc7\u5ea6\u5f52\u56e0\uff1b\u4f46\u96f6\u5ba2\u89c2\u7f13\u89e3\u672c\u8eab\uff0c\u5df2\u7ecf\u8db3\u4ee5\u8ba9\u6cbb\u7597\u6307\u6570\u6253\u4e0a\u95ee\u53f7\u3002<\/p>\n\n\n\n

\u56db\u3001\u6838\u5fc3\u6311\u6218\uff1a\u9009\u62e9\u6027<\/strong><\/h5>\n\n\n\n

\u4e3a\u4ec0\u4e48”\u9009\u62e9\u6027”\u662f\u8fd9\u4e2a\u8d5b\u9053\u552f\u4e00\u7684\u80dc\u8d1f\u624b\uff1f<\/p>\n\n\n\n

Sec61\u901a\u9053\u5bf9\u6b63\u5e38\u7ec6\u80de\u7684\u86cb\u767d\u7a33\u6001\u4e0d\u53ef\u6216\u7f3a\u3002\u5e7f\u8c31\u6291\u5236\u4f1a\u7834\u574f\u7ec4\u6210\u578b\u5206\u6ccc\u9014\u5f84\uff0c\u8bf1\u5bfc\u5185\u8d28\u7f51\u5e94\u6fc0\uff0c\u9020\u6210\u5b9e\u8d28\u6027\u7684\u5728\u9776\u3001\u8131\u7ec4\u7ec7\u6bd2\u6027\u3002\u7b2c\u4e00\u4ee3\u5929\u7136\u4ea7\u7269\u6291\u5236\u5242\u6b63\u662f\u56e0\u4e3a\u5bf9\u5206\u6ccc\u5668\u5b98\u7684\u6bd2\u6027\u800c\u6ca1\u80fd\u8fdb\u5165\u4e34\u5e8a[7]\u3002\u80f0\u817a\u817a\u6ce1\u7ec6\u80de\u3001\u6d46\u7ec6\u80de\u3001\u809d\u7ec6\u80de\u7b49\u9ad8\u5206\u6ccc\u7ec4\u7ec7\u5bf9Sec61\u8f6c\u8fd0\u9ad8\u5ea6\u4f9d\u8d56\uff0c\u5373\u4f7f\u9009\u62e9\u6027\u663e\u8457\u6539\u5584\uff0c\u8fd9\u4e9b\u7ec4\u7ec7\u4ecd\u53ef\u80fd\u5bf9\u90e8\u5206\u901a\u9053\u963b\u65ad\u4fdd\u6301\u654f\u611f\u2014\u2014\u8fd9\u7ed9\u4efb\u4f55\u5b54\u9053\u9776\u5411\u6291\u5236\u5242\u7684\u6700\u5927\u8010\u53d7\u5242\u91cf\u8bbe\u4e86\u4e0a\u9650[7,22]\u3002<\/p>\n\n\n\n

\u6297\u6027\u7a81\u53d8\u65e2\u662f\u8bc1\u636e\uff0c\u4e5f\u662f\u6f5c\u5728\u5de5\u5177<\/strong><\/h6>\n\n\n\n

\u5728HEK293\u7ec6\u80de\u4e2d\uff0cN300A\u7a81\u53d8\u53ef\u8d4b\u4e88\u5bf9KZR-8445\u7684\u6297\u6027\uff1bR66I\u7a81\u53d8\u540c\u6837\u8d4b\u4e88\u6297\u6027\uff0c\u5c3d\u7ba1R66\u5728\u7ed3\u6784\u6a21\u578b\u4e2d\u5e76\u4e0d\u4e0eKZR-8445\u5f62\u6210\u6781\u6027\u63a5\u89e6\uff0c\u63a8\u6d4b\u6e90\u4e8eplug\u87ba\u65cb\u6784\u8c61\u6539\u53d8[9]\u3002Itskanov\u7b49\u5219\u5bf9\u9175\u6bcdSec61\u03b1\u768434\u4e2a\u4f4d\u70b9\u505a\u4e8684\u4e2a\u70b9\u7a81\u53d8\u626b\u63cf\uff0c\u9274\u5b9a\u51fa19\u4e2acotransin CP2\u6297\u6027\u4f4d\u70b9\u548c14\u4e2aipomoeassin F\u6297\u6027\u4f4d\u70b9[8]\u3002\u4eba\u6e90\u7ec6\u80de\u4e2d\u6d4b\u8bd5\u7684\u662fQ127A\u4e0eN300A\uff1a\u4e8c\u8005\u5747\u663e\u8457\u5c06\u6291\u5236\u5242\u7684\u91cf\u6548\u66f2\u7ebf\u53f3\u79fb\uff0c\u4e14N300\u7a81\u53d8\u9020\u6210\u7684\u6297\u6027\u666e\u904d\u5f3a\u4e8eQ127\u2014\u2014\u4e0e\u7ed3\u6784\u4e2dN300\u4fa7\u94fe\u9170\u80fa\u66f4\u76f4\u63a5\u671d\u5411\u6291\u5236\u5242\u76f8\u7b26[9]\u3002\u9700\u8981\u7cbe\u786e\u7684\u4e00\u53e5\uff1a\u76ee\u524d\u516c\u5f00\u7684\u6297\u6027\u7a81\u53d8\u6570\u636e\u4e3b\u8981\u6765\u81ea\u4e34\u5e8a\u524d\u5316\u5408\u7269\uff08KZR-8445\u3001cotransin\u3001decatransin\u3001ipomoeassin F\u3001CADA\uff09\uff0c\u5c1a\u65e0KZR-261\u4e34\u5e8a\u8010\u836f\u682a\u7684\u6d4b\u5e8f\u62a5\u9053[8,9,10]\u3002\u628a\u8fd9\u4e9b\u4f4d\u70b9\u4f5c\u4e3a\u4e34\u5e8a\u6d4b\u5e8f\u76d1\u6d4b\u6807\u5fd7\u7269\u662f\u4e00\u4e2a\u5408\u7406\u8bbe\u60f3\uff0c\u4f46\u4ecd\u662f\u8bbe\u60f3\u3002<\/p>\n\n\n\n

\u4e94\u3001\u4ea7\u4e1a\u683c\u5c40\uff1a\u4e00\u4e2a\u6539\u836f\uff0c\u4e00\u4e2a\u6539\u95e8<\/strong><\/h5>\n\n\n\n
\u8f89\u745e<\/strong> \u00d7 <\/strong>Enodia<\/strong>\uff1a\u4ece<\/strong>\u836f\u7269\u7aef\u505a\u9009\u62e9<\/strong><\/h6>\n\n\n\n

\u8f89\u745e\u4e0eEnodia\u7684\u4ea4\u6613\u603b\u989d\u8d85\u8fc75\u4ebf\u7f8e\u5143\u3002Enodia\u8d1f\u8d23\u7b5b\u9009\u3001\u4f18\u5316\u548c\u5f00\u53d1\u5019\u9009\u836f\u7269\uff0c\u8f89\u745e\u627f\u62c5\u4e34\u5e8a\u7814\u7a76\u3001\u751f\u4ea7\u3001\u76d1\u7ba1\u548c\u5546\u4e1a\u5316[1,2]\u3002Enodia\u7684\u5e73\u53f0\u6574\u5408\u4e86\u86cb\u767d\u8d28\u7ec4\u5b66\u3001\u51b7\u51bb\u7535\u955c\u548c\u5b9a\u5236\u7ec6\u80de\u7cfb\u5e93\uff0c\u53e0\u52a0\u673a\u5668\u5b66\u4e60\u8bbe\u8ba1\u5f15\u64ce\uff0c\u521d\u671f\u805a\u7126\u708e\u75c7\u3001\u514d\u75ab\u5b66\u548c\u80bf\u7624\u5b66[1]\u3002\u8fd9\u5bb6\u516c\u53f82025\u5e742\u6708\u7531Argobio\u548c\u5df4\u65af\u5fb7\u7814\u7a76\u6240\u5b75\u5316\uff0c\u8f89\u745e\u521b\u6295\u53c2\u4e0e\u51762070\u4e07\u6b27\u5143\uff08\u7ea62500\u4e07\u7f8e\u5143\uff09\u79cd\u5b50\u8f6e[1,18]\u3002<\/p>\n\n\n\n

\u793c\u6765<\/strong> \u00d7 Gate Bioscience<\/strong>\uff1a\u4ece<\/strong>\u5e95\u7269\u7aef\u505a\u9009\u62e9<\/strong><\/h6>\n\n\n\n

2026\u5e7410\u67085\u65e5\uff0c\u793c\u6765\u8ffd\u52a08.7\u4ebf\u7f8e\u5143\uff1b\u6b64\u524d2025\u5e74\u7684\u539f\u59cb\u534f\u8bae\u4ef7\u503c\u6700\u9ad88.56\u4ebf\u7f8e\u5143\u3002\u4e24\u7b14\u534f\u8bae\u9488\u5bf9\u7684\u9776\u70b9\u4e0d\u540c\uff0c\u5408\u5e76\u8ba1\u7b97\u4f7f\u793c\u6765\u4e0eGate\u7684\u5408\u4f5c\u603b\u6f5c\u5728\u4ef7\u503c\u7ea6\u8fbe17\u4ebf\u7f8e\u5143[3,4]\u3002Gate\u7684”\u5206\u5b50\u95e8”\u662f\u53e3\u670d\u5c0f\u5206\u5b50\uff0cCEO Jordi Mata-Fink\u7684\u6bd4\u55bb\u662f”bouncer at the door checking IDs”\uff08\u5728\u95e8\u53e3\u67e5\u8eab\u4efd\u8bc1\u7684\u4fdd\u5b89\uff09[3]\u3002Gate\u6210\u7acb\u4e8e2021\u5e74\uff0c\u6700\u5148\u8fdb\u7684\u5185\u90e8\u8d44\u4ea7\u9488\u5bf9\u670a\u75c5\u6bd2\u75c5\uff0c\u58f0\u79f0\u5e73\u53f0\u53ef\u8986\u76d6\u7ea64000\u4e2a\u86cb\u767d\u9776\u70b9[3]\u3002\u793c\u6765\u57282025\u5e7411\u6708Gate\u76846500\u4e07\u7f8e\u5143B\u8f6e\u878d\u8d44\u4e2d\u4f5c\u4e3a\u65b0\u6295\u8d44\u65b9\u53c2\u4e0e\uff0c\u8be5\u8f6e\u7531Forbion\u9886\u6295[19]\u3002<\/p>\n\n\n\n

\u8868\u9762\u90fd\u662f<\/strong>“<\/strong>\u9009\u62e9\u6027<\/strong>“<\/strong>\uff0c\u5185\u6838\u5b8c\u5168\u4e0d\u540c<\/strong><\/h6>\n\n\n\n
 <\/td>Enodia<\/strong><\/td>Gate Bioscience<\/strong><\/td><\/tr>
\u5207\u5165\u70b9<\/td>\u836f\u7269\u7aef<\/td>\u5e95\u7269\u7aef<\/td><\/tr>
\u505a\u6cd5<\/td>\u7528\u673a\u5668\u5b66\u4e60\u8bbe\u8ba1\u4fe1\u53f7\u80bd\u4fe1\u606f\u9a71\u52a8\u7684\u5c0f\u5206\u5b50\uff0c\u6539\u9020\u5206\u5b50\u4f7f\u5176\u5bf9\u7279\u5b9a\u5ba2\u6237\u86cb\u767d\u7684\u4fe1\u53f7\u80bd\u654f\u611f[1]<\/td>\u5206\u5b50\u95e8\u8bc6\u522b\u81f4\u75c5\u86cb\u767d\u4e0a\u7684\u72ec\u7279\u5e8f\u5217\u7279\u5f81\uff0c\u5728\u901a\u9053\u53e3\u62e6\u622a[3]<\/td><\/tr>
\u672c\u8d28<\/td>cotransin\uff0fKZR-9873\u8def\u7ebf\u7684\u5ef6\u4f38[1,13]<\/td>\u7ed9\u901a\u9053\u88c5\u4e00\u4e2a”\u8bc6\u522b\u5668”[3]<\/td><\/tr>
\u5242\u578b<\/td>\u672a\u516c\u5f00\uff08Kezar\u8d44\u4ea7\u4e3a\u9759\u8109\u7ed9\u836f\uff09[10]<\/td>\u53e3\u670d\u5c0f\u5206\u5b50[3]<\/td><\/tr>
\u5e7f\u5ea6<\/td>\u5148\u505a\u708e\u75c7\uff0f\u514d\u75ab\uff0f\u80bf\u7624\uff0c\u53ef\u62d3\u75c5\u6bd2\u5b66[1]<\/td>\u7ea64000\u4e2a\u9776\u70b9\uff0c”\u75be\u75c5\u4e0d\u53ef\u77e5\u6a21\u6001”[3]<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

\u4e00\u4e2a\u6539\u836f\uff0c\u4e00\u4e2a\u6539\u95e8\u3002<\/strong>\u8fd9\u6b63\u662f”\u4e24\u79cd\u7b56\u7565\u90fd\u5728\u8bd5\u56fe\u89e3\u7b54\u540c\u4e00\u4e2a\u95ee\u9898”\u7684\u5177\u4f53\u7b54\u6848\u3002<\/p>\n\n\n\n

\u516d\u3001\u53c2\u7167\u7cfb\uff1a\u9996\u6b3e<\/strong>PROTAC<\/strong>\u5df2\u7ecf\u8dd1<\/strong>\u901a\u5546\u4e1a\u95ed\u73af<\/strong><\/h5>\n\n\n\n

\u8bc4\u4ef7Sec61\u8fd9\u7c7b\u65b0\u6a21\u6001\uff0c\u6709\u4e00\u4e2a\u73b0\u6210\u7684\u5750\u6807\u30022026\u5e745\u67081\u65e5\uff0c\u9996\u6b3ePROTAC\u7c7b\u83b7\u6279\u836f\u7269vepdegestrant\uff08Veppanu\uff09\u83b7FDA\u6279\u51c6\uff0c\u7528\u4e8e\u7ecf\u81f3\u5c11\u4e00\u7ebf\u5185\u5206\u6ccc\u6cbb\u7597\u540e\u8fdb\u5c55\u7684ER\u9633\u6027\uff0fHER2\u9634\u6027\u3001ESR1\u7a81\u53d8\u7684\u665a\u671f\u6216\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u6210\u4eba\u60a3\u8005\uff0c\u540c\u65f6\u6279\u51c6Guardant360 CDx\u4f5c\u4e3a\u4f34\u968f\u8bca\u65ad[20,21]\u3002\u7597\u6548\u6570\u636e\uff1aESR1\u7a81\u53d8\u4eba\u7fa4\u4e2d\u4f4dPFS 5\u4e2a\u6708 vs \u6c1f\u7ef4\u53f8\u7fa42.1\u4e2a\u6708\uff08HR 0.57\uff09\uff0cORR 19% vs 4%[21]\u3002\u5546\u4e1a\u5316\u4e5f\u5df2\u843d\u5730\uff1aArvinas\u4e0e\u8f89\u745e\u4e8e2026\u5e745\u6708\u9009\u5b9aRigel Pharmaceuticals\u7b7e\u7f72\u5168\u7403\u72ec\u5bb6\u8bb8\u53ef\uff087000\u4e07\u7f8e\u5143\u9996\u4ed8\u6b3e + 1500\u4e07\u7f8e\u5143\u8fc7\u6e21\u6b3e\uff0c\u6700\u9ad83.2\u4ebf\u7f8e\u5143\u91cc\u7a0b\u7891\uff09\uff0c\u534f\u8bae6\u6708\u751f\u6548\uff0c8\u6708\u4e2d\u65ecVEPPANU\u5df2\u5728\u7f8e\u56fd\u6b63\u5f0f\u5546\u4e1a\u4f9b\u5e94\uff1b5\u67088\u65e5NCCN\u4e73\u817a\u764c\u6307\u5357\u5c06\u5176\u6536\u5f55\u4e3a2A\u7c7b\u63a8\u8350[21]\u3002<\/p>\n\n\n\n

\u53e6\u4e00\u4e2a\u503c\u5f97\u8bb0\u4e0b\u7684\u65b9\u5411\uff1a\u5728\u654f\u611f\u7684\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u7ec6\u80de\u7cfbH929\u4e2d\uff0cKZR-834<\/strong>\u4e0e\u86cb\u767d\u9176\u4f53\u6291\u5236\u5242carfilzomib\u8054\u7528\u663e\u793a\u5f3a\u534f\u540c\u6548\u5e94\uff0c\u591a\u4e2a\u6d53\u5ea6\u4e0b\u7684Bliss independence\u503c\u5747\u8d85\u8fc70.25\uff1b\u5728\u76f8\u5bf9\u8010\u836f\u7684U266\u7ec6\u80de\u4e2d\uff0ccarfilzomib\u8054\u5408\u65b9\u6848\u540c\u6837\u4ea7\u751f\u4e86\u589e\u5f3a\u6548\u5e94\uff0c\u514b\u670d\u4e86\u5176\u5bf9Sec61\u6291\u5236\u7684\u5355\u836f\u76f8\u5bf9\u8010\u836f[10]\u3002\u5b83\u4e3a\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u7b49\u6d46\u7ec6\u80de\u6027\u80bf\u7624\u7684\u9002\u5e94\u75c7\u9009\u62e9\u63d0\u4f9b\u4e86\u673a\u5236\u4f9d\u636e[10]\u3002<\/p>\n\n\n\n

\u4e03\u3001\u63a8\u8fdb\u4e34\u5e8a\uff0c\u4e94<\/strong>\u4e2a\u8981\u7d20<\/strong>\u9700\u8981\u5148\u60f3\u6e05\u695a<\/strong><\/h5>\n\n\n\n
\u7b2c\u4e00\uff0c<\/strong>PD<\/strong>\u6807\u5fd7\u7269\u662f\u9996\u8981\u4efb\u52a1<\/strong><\/h6>\n\n\n\n

Sec61\u6291\u5236\u5242\u4e0d\u76f4\u63a5\u7ed3\u5408\u9776\u86cb\u767d\uff0c\u4f20\u7edf\u7684\u53d7\u4f53\u5360\u6709\u7387\u6d4b\u5b9a\u4e0d\u9002\u7528\u3002\u9700\u8981\u5f00\u53d1\u57fa\u4e8e\u86cb\u767d\u8d28\u7ec4\u5b66\u7684\u5ba2\u6237\u86cb\u767d\u6291\u5236\u8c31\uff0c\u4ee5\u53ca\u4fe1\u53f7\u80bd\u62a5\u544a\u57fa\u56e0\u5206\u6790\uff0c\u5728I\u671f\u5242\u91cf\u9012\u589e\u4e2d\u56de\u7b54”\u6291\u5236\u4e86\u591a\u5c11\u5ba2\u6237\u86cb\u767d”\u4e0e”\u4e34\u5e8a\u83b7\u76ca\uff0f\u6bd2\u6027”\u4e4b\u95f4\u7684\u5173\u7cfb[10,14]\u3002<\/p>\n\n\n\n

\u7b2c\u4e8c\uff0c\u6297\u6027\u7a81\u53d8\u76d1\u6d4b\u9700\u8981\u63d0\u524d\u89c4\u5212<\/strong><\/h6>\n\n\n\n

Sec61\u03b1\u7684N300\u548cQ127\u4f4d\u70b9\u662f\u5df2\u77e5\u7684\u6291\u5236\u5242\u7ed3\u5408\u5173\u952e\u6b8b\u57fa\uff0c\u53ef\u5728\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\u8d4b\u4e88\u6297\u6027[8,9]\u3002\u4f46\u76ee\u524d\u516c\u5f00\u7684\u6297\u6027\u6570\u636e\u5168\u90e8\u6765\u81ea\u4e34\u5e8a\u524d\u5316\u5408\u7269\uff0c\u5c1a\u65e0KZR-261\u4e34\u5e8a\u8010\u836f\u682a\u7684\u6d4b\u5e8f\u62a5\u9053[10]\u3002\u5982\u679c\u8981\u5728I\u671f\u7eb3\u5165ctDNA\u76d1\u6d4b\uff0c\u68c0\u6d4bpanel\u548c\u91c7\u6837\u65f6\u95f4\u70b9\u9700\u8981\u524d\u7f6e\u8bbe\u8ba1\u3002<\/p>\n\n\n\n

\u7b2c\u4e09\uff0c\u7ed9\u836f\u9014\u5f84\u662f\u8054\u5408\u65b9\u6848\u7684\u8bbe\u8ba1\u53d8\u91cf<\/strong><\/h6>\n\n\n\n

KZR-261\u4e3a\u9759\u8109\u7ed9\u836f[10]\uff0cGate\u7684\u5206\u5b50\u95e8\u5b9a\u4f4d\u4e3a\u53e3\u670d[3]\u3002\u5982\u679c\u8ba1\u5212\u4e0ePD-1\u6297\u4f53\u8054\u7528\uff0c\u53e3\u670d\u7ed9\u836f\u5141\u8bb8\u66f4\u7075\u6d3b\u7684\u5242\u91cf\u8c03\u6574\u548c\u957f\u671f\u7ef4\u6301\uff0c\u800c\u9759\u8109\u7ed9\u836f\u53ef\u80fd\u9650\u5236\u8054\u5408\u65b9\u6848\u7684\u7ed9\u836f\u9891\u7387\u3002<\/p>\n\n\n\n

\u7b2c\u56db\uff0c\u9002\u5e94\u75c7<\/strong>\u9700\u8981\u4ece\u6cdb\u5b9e\u4f53\u7624<\/strong>\u8f6c\u5411\u66f4\u5177\u751f\u7269\u5b66\u4f9d\u636e\u7684\u573a\u666f<\/strong><\/h6>\n\n\n\n

\u96f6\u5ba2\u89c2\u7f13\u89e3\u8bf4\u660e\uff0c\u5728\u672a\u7ecf\u9009\u62e9\u7684\u5b9e\u4f53\u7624\u4eba\u7fa4\u4e2d\u5355\u836f\u6d3b\u6027\u6709\u9650[6]\u3002\u66f4\u5177\u6f5c\u529b\u7684\u65b9\u5411\u5305\u62ec\u6d46\u7ec6\u80de\u6027\u80bf\u7624\uff08Sec61\u6291\u5236\u4e0e\u86cb\u767d\u9176\u4f53\u6291\u5236\u5242\u7684\u534f\u540c\u903b\u8f91[10]\uff09\u548cPD-1\u8054\u7528\u2014\u2014\u8fd9\u4e9b\u573a\u666f\u9700\u8981\u5728\u65b9\u6848\u8bbe\u8ba1\u9636\u6bb5\u5c31\u9884\u8bbe\u60a3\u8005\u5bcc\u96c6\u7b56\u7565\u3002<\/p>\n\n\n\n

\u7b2c\u4e94\uff0c\u9ad8\u5206\u6ccc\u7ec4\u7ec7\u7684\u957f\u671f\u5b89\u5168\u6027\u76d1\u6d4b\u8981\u5355\u72ec\u8bbe\u8ba1<\/strong><\/h6>\n\n\n\n

\u80f0\u817a\u3001\u809d\u810f\u7b49\u9ad8\u5206\u6ccc\u6d3b\u6027\u5668\u5b98\u7684\u957f\u671f\u529f\u80fd\u76d1\u6d4b\uff0c\u5e94\u4f5c\u4e3a\u72ec\u7acb\u7684\u5b89\u5168\u6027\u7ec8\u70b9\u7eb3\u5165\u65b9\u6848\uff0c\u53ea\u662f\u585e\u8fdb\u5e38\u89c4\u809d\u80be\u529f\u80fd\u9762\u677f\u662f\u4e0d\u591f\u7684[7,22]\u3002<\/p>\n\n\n\n

Sec61<\/strong>\u6291\u5236\u5242\u9762\u4e34\u7684\u6838\u5fc3\u6311\u6218<\/strong>\uff0c<\/strong>\u4e0d<\/strong>\u4ec5\u662f<\/strong>\u79d1\u5b66\u6982\u5ff5\u95ee\u9898\uff0c<\/strong>\u66f4<\/strong>\u662f\u9009\u62e9\u6027\u5de5\u7a0b\u95ee\u9898\u3002<\/strong>\u4e00\u5bb6\u88ab\u505c\u6389\u7684I\u671f\u3001\u96f6\u5ba2\u89c2\u7f13\u89e3\u7684\u4e34\u5e8a\u6570\u636e\uff0c\u6ca1\u6709\u5413\u9000\u8f89\u745e\u548c\u793c\u6765\u2014\u2014\u56e0\u4e3a”\u5728\u5408\u6210\u4f4d\u70b9\u62e6\u622a”\u8fd9\u6761\u8def\uff0c\u786e\u5b9e\u6253\u5f00\u4e86\u4e00\u6279PROTAC\u591f\u4e0d\u7740\u7684\u9776\u70b9[1,2,3,4]\u3002Enodia\u6539\u836f\uff0cGate\u6539\u95e8\u3002\u5b83\u4eec\u90fd\u5728\u56de\u7b54\u540c\u4e00\u4e2a\u95ee\u9898\uff1a\u5982\u4f55\u5728Sec61\u8fd9\u6761\u5171\u4eab\u901a\u9053\u4e0a\u5b9e\u73b0\u8db3\u591f\u7684\u9009\u62e9\u6027\uff0c\u540c\u65f6\u628a\u6cbb\u7597\u7a97\u53e3\u7559\u5728\u53ef\u63a5\u53d7\u7684\u8303\u56f4\u91cc\u3002<\/p>\n\n\n\n

\u53c2\u8003\u6587\u732e<\/strong><\/h5>\n\n\n\n

[1] Enodia Therapeutics Announces Research Collaboration and License Agreement with Pfizer to Develop Sec61-Targeting Small Molecules. Business Wire \/ AFP, 2026-10-13.<\/p>\n\n\n\n

[2] Pfizer inks $500M Enodia pact to join Lilly in emerging protein degrader field. Fierce Biotech, 2026-10-13.<\/p>\n\n\n\n

[3] Gate CEO sees expanded $870M pact with Lilly as \u2018vote of confidence\u2019 in biotech\u2019s platform. Fierce Biotech, 2026-10-05.<\/p>\n\n\n\n

[4] Lilly and Gate agree $870m deal for molecular gate medicines. Drug Discovery World, 2026-10-09.<\/p>\n\n\n\n

[5] Kezar stalls solid tumour trial to focus on autoimmune disease candidate. Clinical Trials Arena, 2024-08-14.<\/p>\n\n\n\n

[6] KZR-261 Phase 1 Clinical Trial (NCT05047536). ClinicalTrials.gov\uff1b\u53ca Kezar Life Sciences 2024\u5e74\u7b2c\u4e8c\u5b63\u5ea6\u8d22\u52a1\u4e0e\u4e1a\u52a1\u66f4\u65b0\uff0861\u4f8b\u5165\u7ec4\u3001\u65e0\u5ba2\u89c2\u7f13\u89e3\u30015\u4f8bSD\u22654\u4e2a\u6708\u30012\u4f8bSD\u226512\u4e2a\u6708\uff09\u3002<\/p>\n\n\n\n

[7] Xin J, Yin K, Li S, Gu P, Shao S. Exploring the ER channel protein Sec61: recent advances in pathophysiological significance and novel pharmacological inhibitors. Front Pharmacol. 2025;16:1580086. PMID: 40535761.<\/p>\n\n\n\n

[8] Itskanov S, Wang L, Junne T, et al. A common mechanism of Sec61 translocon inhibition by small molecules. Nat Chem Biol. 2023;19(9):1063-1071. DOI: 10.1038\/s41589-023-01337-y. PMID: 37169959.<\/p>\n\n\n\n

[9] Rehan S, Tranter D, Sharp PP, et al. Signal peptide mimicry primes Sec61 for client-selective inhibition. Nat Chem Biol. 2023;19(9):1054-1062. DOI: 10.1038\/s41589-023-01326-1. PMID: 37169961. PDB: 7ZL3.<\/p>\n\n\n\n

[10] Lowe E, Anderl JL, Bade D, et al. Preclinical characterization of novel multi-client inhibitors of Sec61 with broad antitumor activity. J Pharmacol Exp Ther. 2025;392(8):103634. DOI: 10.1016\/j.jpet.2025.103634. PMID: 40669140.<\/p>\n\n\n\n

[11] Hao Q, Wang L, Pan H, et al. Structure-based design of Sec61 translocon targeting prodrugs minimize off-target toxicity. Cell Chem Biol. 2026;33(6):823-836.e21. DOI: 10.1016\/j.chembiol.2026.05.006. PMID: 42263680. PDB: 9YWS, EMDB: EMD-73558.<\/p>\n\n\n\n

[12] Tian H, Pan W, Shi H, et al. Coibamide Analogue as a Novel-Class Payload for Antibody-Drug Conjugate. J Med Chem. 2026;69(5):5691-5702. DOI: 10.1021\/acs.jmedchem.5c02941.<\/p>\n\n\n\n

[13] Wenzell NA, Tuch BB, McMinn DL, Lyons MJ, Kirk CJ, Taunton J. Global signal peptide profiling reveals principles of selective Sec61 inhibition. Nat Chem Biol. 2024;20(9):1154-1163. DOI: 10.1038\/s41589-024-01592-7. PMID: 38519575.<\/p>\n\n\n\n

[14] Qian Y, Whang J, Anderl J, et al. Quantitative proteomic profiling of novel anti-cancer small molecule inhibitors of Sec61: Mechanistic investigation and biomarker discovery. Cancer Res. 2021;81(13_Supplement):Abstract 323. AACR Annual Meeting 2021.<\/p>\n\n\n\n

[15] Asset Purchase Agreement between Enodia Therapeutics SAS and Kezar Life Sciences, Inc. March 6, 2026. SEC Form 8-K.<\/p>\n\n\n\n

[16] Enodia Therapeutics Strengthens Sec61 Portfolio Through Acquisition of Preclinical Assets from Kezar Life Sciences. Business Wire, 2026-03-12.<\/p>\n\n\n\n

[17] Aurinia Pharmaceuticals to Acquire Kezar Life Sciences. March 30, 2026\uff1b\u6536\u8d2d\u4e8e2026\u5e745\u670811\u65e5\u5b8c\u6210\uff08Aurinia 10-Q, 2026-06-30\uff1bNasdaq Trader ECA2026-307\uff09\u3002<\/p>\n\n\n\n

[18] Institut Pasteur. Enodia Therapeutics: \u20ac20.7 million in funding to translate Institut Pasteur discovery into innovative therapies. 2026-01-15.<\/p>\n\n\n\n

[19] Forbion Leads $65 Million Series B Financing in Gate Bioscience. November 13, 2025.<\/p>\n\n\n\n

[20] FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. U.S. Food and Drug Administration, 2026-05-01.<\/p>\n\n\n\n

[21] The PROTAC milestone: FDA approval of vepdegestrant (ARV-471) for ESR1-mutated breast cancer. ScienceDirect, 2026-08-15.<\/p>\n\n\n\n

[22] Advances in SEC61G research: from ER translocon subunit to emerging pan-cancer oncogenic roles. Cancer Biol Ther. 2026. DOI: 10.1080\/15384047.2026.2694136.\uff08\u540c\u884c\u8bc4\u8bae\u7efc\u8ff0\uff1bKZR-261\u7ea62%\u20135%\u5ba2\u6237\u86cb\u767d\u6291\u5236\u3001apratoxin A\u7f3a\u4e4f\u5e95\u7269\u9009\u62e9\u6027\u3001\u9ad8\u5206\u6ccc\u7ec4\u7ec7MTD\u4e0a\u9650\u7b49\u8868\u8ff0\u51fa\u5904\uff09<\/p>\n\n\n\n

[23] Lowe E, Fan RA, Jiang J, et al. Preclinical evaluation of KZR-261, a novel small molecule inhibitor of Sec61. J Clin Oncol. 2020;38(15_suppl):Abstract 3582. DOI: 10.1200\/JCO.2020.38.15_suppl.3582. ASCO Annual Meeting 2020.<\/p>\n\n\n\n

\u514d\u8d23\u58f0\u660e\uff1a\u672c\u6587\u4e0d\u6784\u6210\u6295\u8d44\u5efa\u8bae\u6216\u533b\u7597\u5efa\u8bae\u3002\u6240\u5f15\u6570\u636e\u5747\u4ee5\u53c2\u8003\u6587\u732e\u4e3a\u51c6\u3002<\/p>\n\n\n\n

<\/p>\n\n\n\n

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