{"id":53694,"date":"2018-09-27T01:00:00","date_gmt":"2018-09-30T01:48:04","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/09\/30\/%e6%b7%b1%e5%ba%a6%e9%98%85%e8%af%bb%ef%bc%8c%e4%b9%b3%e8%85%ba%e7%99%8c%e6%bd%9c%e5%8a%9b%e9%9d%b6%e7%82%b9cdk4-6%e8%b0%83%e7%a0%94%e6%8a%a5%e5%91%8a\/"},"modified":"2018-09-30T09:48:11","modified_gmt":"2018-09-30T01:48:11","slug":"%e6%b7%b1%e5%ba%a6%e9%98%85%e8%af%bb%ef%bc%8c%e4%b9%b3%e8%85%ba%e7%99%8c%e6%bd%9c%e5%8a%9b%e9%9d%b6%e7%82%b9cdk4-6%e8%b0%83%e7%a0%94%e6%8a%a5%e5%91%8a","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/53694\/","title":{"rendered":"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a"},"content":{"rendered":"
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\u5f15\u8a00 <\/span><\/strong>\u7ec6\u80de\u5468\u671f\u7684\u5931\u8c03\u662f\u80bf\u7624\u751f\u957f\u548c\u8f6c\u79fb\u7684\u5178\u578b\u6807\u5fd7\u4e4b\u4e00\uff0c\u901a\u8fc7<\/span>CDK\u6291\u5236\u5242\u91cd\u65b0\u5efa\u7acb\u7ec6\u80de\u5468\u671f\u7684\u8c03\u63a7\u5728\u80bf\u7624\u9776\u5411\u6cbb\u7597\u7684\u53d1\u5c55\u4e2d\u5df2\u7ecf\u6210\u4e3a\u6709\u5438\u5f15\u529b\u7684\u65b9\u5411\u3002<\/span><\/span>CDK4\/6\u6291\u5236\u5242\u4e5f\u662f\u4e73\u817a\u764c\u6700\u5177\u6f5c\u529b\u7684\u9776\u70b9\u4e4b\u4e00\uff0c<\/span><\/strong>\u5df2\u88ab\u8bc1\u660e\u5728\u6cbb\u7597\u665a\u671f\u96cc\u6fc0\u7d20\u53d7\u4f53\u9633\u6027\uff0c<\/span>HER2\u9634\u6027\u4e73\u817a\u764c\u65b9\u9762\u6700\u4e3a\u6709\u6548\u3002\u4e0e\u6fc0\u7d20\u963b\u65ad\u836f\u7269\u8054\u5408\uff0c<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\uff08\u5305\u62ec<\/span>palbociclib<\/span>\uff0c<\/span>ribociclib\u548cabemaciclib<\/span>\uff09\u5df2\u663e\u7740\u6539\u5584\u4e86\u8be5\u7c7b\u60a3\u8005\u7684\u65e0\u8fdb\u5c55\u751f\u5b58\u671f\u548c\u7f13\u89e3\u7387\u3002\u5f53\u524d\u7684\u7814\u7a76\u8868\u660e<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\u4e0e\u5185\u5206\u6ccc\u836f\u7269\u8054\u5408\u6cbb\u7597\u6fc0\u7d20\u53d7\u4f53\u9633\u6027\u4e73\u817a\u764c\u662f\u4e00\u4e2a\u65b0\u7684\u6807\u51c6\u3002<\/span><\/span><\/span><\/p>\n<\/section>\n

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\u4e73\u817a\u764c\u662f\u5728\u4e73\u817a\u4e0a\u76ae\u7ec4\u7ec7\u51fa\u73b0\u7684\u6076\u6027\u80bf\u7624<\/span>,\u76ee\u524d\u4e73\u817a\u764c\u5df2\u6210\u4e3a\u5a01\u80c1\u5973\u6027\u8eab\u5fc3\u5065\u5eb7\u7684\u5e38\u89c1\u80bf\u7624\u548c\u7b2c\u4e00<\/span>\u201c<\/span>\u6740\u624b<\/span>\u201d<\/span>\uff0c\u5176\u53d1\u75c5\u7387\u5728\u9010\u5e74\u4e0a\u5347\uff0c\u4e14\u5177\u6709\u5e74\u8f7b\u5316\u7684\u8d8b\u52bf\u3002<\/span>\u4e73\u817a\u764c\u5728\u5168\u4e16\u754c\u5973\u6027\u764c\u75c7\u4e2d\u53d1\u75c5\u7387\u6700\u9ad8<\/span><\/strong>\uff08\u56fe\u4e00\uff09\uff0c<\/span><\/strong>\u7f8e\u56fd\u764c\u75c7\u4e2d\u5fc3\u548c\u4e2d\u56fd\u56fd\u5bb6\u764c\u75c7\u4e2d\u5fc3\u6700\u65b0\u53d1\u5e03\u7684\u6570\u636e\u663e\u793a\uff0c\u4e2d\u7f8e\u5973\u6027\u53d1\u75c5\u7387\u6700\u9ad8\u7684\u6076\u6027\u80bf\u7624\u5747\u4e3a\u4e73\u817a\u764c\u3002\u7f8e\u56fd\u764c\u75c7\u4e2d\u5fc3\u9884\u8ba1\uff0c<\/span>2018\u5e74\u7f8e\u56fd\u5c06\u6709<\/span>266120<\/span>\u540d\u5973\u6027\u4e73\u817a\u764c\u65b0\u53d1\u75c5\u4f8b\uff0c\u5360\u6240\u6709\u65b0\u53d1\u764c\u75c7\u75c5\u4f8b\u6570\u7684<\/span>30%<\/span>\uff1b\u4e2d\u56fd\u5973\u6027\u4e73\u817a\u764c\u7684\u53d1\u75c5\u7387\u5360\u6240\u6709\u764c\u75c7\u7684<\/span>17.07%<\/span>\u3002\u901a\u8fc7\u957f\u671f\u7684\u5065\u5eb7\u5ba3\u6559\u548c\u65e9\u7b5b\u65e9\u8bca\uff0c<\/span><\/span>\u4e2d\u56fd\u4e73\u817a\u764c\u7684\u4e34\u5e8a\u8bca\u7597\u53d6\u5f97\u4e86\u5de8\u5927\u7684\u7a81\u7834\uff0c\u66f4\u591a\u7684\u60a3\u8005\u5728\u75be\u75c5\u65e9\u671f\u9636\u6bb5\u88ab\u53d1\u73b0\u5e76\u83b7\u5f97\u53ca\u65f6\u7684\u6cbb\u7597\uff0c\u4f46\u4ecd\u6709\u7ea630-40%\u7684\u65e9\u671f\u60a3\u8005\u53d1\u5c55\u4e3a\u665a\u671f\u8f6c\u79fb\u6027\u4e73\u817a\u764c<\/span>[1]<\/span><\/sup>\uff1b\u6b64\u5916\uff0c5-10%\u7684\u60a3\u8005\u521d\u8bca\u65f6\u5373\u4e3a\u665a\u671f\u8f6c\u79fb\u6027\u4e73\u817a\u764c<\/span>[1]<\/span><\/sup>\u3002<\/span><\/p>\n


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\u4f17\u6240\u5468\u77e5\uff0c\u665a\u671f\u4e73\u817a\u764c\u901a\u5e38\u65e0\u6cd5\u6cbb\u6108\uff0c\u4e2d\u4f4d\u751f\u5b58\u671f\u4e3a<\/span>2-3\u5e74\uff0c\u4ec5<\/span>5-10%<\/span>\u7684\u60a3\u8005\u80fd\u5b58\u6d3b<\/span>5<\/span>\u5e74<\/span>[1]<\/span><\/sup>\uff1b\u6211\u4eec\u7684\u6cbb\u7597\u76ee\u6807\u662f\u5c3d\u53ef\u80fd\u5ef6\u957f\u60a3\u8005\u6709\u8d28\u91cf\u7684\u751f\u5b58\u671f\u3002<\/span><\/span><\/p>\n


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\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


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\u56fe\u4e2d\u4e0d\u540c\u989c\u8272\u4ee3\u8868\u5168\u7403\u5973\u6027\u9ad8\u53d1\u764c\u75c7\u7684\u5206\u5e03\uff0c\u5176\u4e2d\u7c89\u8272\u4ee3\u8868\u4e73\u817a\u764c\uff0c\u6a59\u8272\u4ee3\u8868\u5bab\u9888\u764c\uff0c\u9ec4\u8272\u4ee3\u8868\u809d\u764c\uff0c\u84dd\u8272\u4ee3\u8868\u80ba\u764c\uff0c\u7eff\u8272\u4ee3\u8868\u7532\u72b6\u817a\u764c\u3002\u6570\u5b57\u8868\u793a\u5168\u7403\u5973\u6027\u9ad8\u53d1\u764c\u75c7\u5206\u5e03\u7684\u56fd\u5bb6\u6216\u5730\u533a\u6570\u3002<\/span><\/o:p><\/span><\/p>\n


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\u4e73\u817a\u764c\u7684\u53d1\u75c5\u56e0\u7d20<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n


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\u4e73\u817a\u764c<\/span><\/strong>\u6709\u5185\u5728\u9057\u4f20\u65b9\u9762\u7684\uff0c\u5982\u57fa\u56e0\u7a81\u53d8\uff1b\u4e5f<\/span> \u6709\u73af\u5883\u65b9\u9762\u7684\uff0c\u5982\u66b4\u9732\u4e8e\u5404\u79cd\u6709\u5bb3\u7684\u5316\u5b66\u7269\u8d28\u3001\u7269\u7406\u8f90\u5c04\u548c<\/span> \u75c5\u6bd2\u4fb5\u5bb3\uff1b\u8fd8\u6709\u751f\u6d3b\u65b9\u5f0f\u3001\u5a5a\u80b2\u72b6\u51b5\u548c\u996e\u98df\u7b49\u65b9\u9762\u7684\u3002\u5a5a\u80b2\u3001<\/span> \u81b3\u98df\u548c\u9057\u4f20\u3002<\/span><\/span>\u5176\u4e2d<\/span><\/strong>\u4e73\u817a\u764c<\/span><\/strong>\u96cc\u6fc0\u7d20\u9ad8\u662f<\/span><\/strong>\u81f4\u75c5\u7684\u4e3b\u8981\u56e0\u7d20<\/span><\/strong>\uff0c\u4e73\u817a\u764c\u5c5e\u6fc0\u7d20\u4f9d\u8d56\u6027\u80bf\u7624\uff0c\u96cc\u6fc0\u7d20\u5728\u5973\u6027\u4e73\u817a\u764c\u7684\u53d1\u75c5\u4e2d\u626e\u6f14\u4e86\u975e\u5e38\u91cd\u8981\u7684\u89d2\u8272\u3002\u4f53\u5185\u7684\u96cc\u6fc0\u7d20\u6c34\u5e73\u5f71\u54cd\u4e73\u817a\u764c\u7684\u53d1\u751f\u3001\u53d1\u5c55\uff0c\u7ea6\u6709<\/span>2\/3\u7684\u4e73\u817a\u764c\u548c\u4f53\u5185\u6fc0\u7d20\u6c34\u5e73\u6709\u5173\u3002\u5927\u91cf\u8fdb\u5165\u4e73\u817a\u7ec4\u7ec7\u7684\u96cc\u6fc0\u7d20\u4f1a\u5728\u4e73\u817a\u7ec4\u7ec7\u4e2d\u5f15\u8d77\u5404\u79cd\u53cd\u5e94\uff0c\u5176\u4e2d\u5c31\u5305\u62ec\u4f7f\u4e73\u817a\u7ec4\u7ec7\u589e\u751f\u3002\u6700\u7ec8\uff0c\u5c31\u6709\u53ef\u80fd\u5bfc\u81f4\u4e73\u817a\u764c\u7684\u53d1\u751f\u3002<\/span><\/span><\/p>\n


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\u4e73\u817a\u764c<\/span><\/strong>\u6cbb\u7597<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n

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\u4e73\u817a\u764c\u662f\u4e00\u7c7b\u5728\u5206\u5b50\u6c34\u5e73\u4e0a\u9ad8\u5ea6\u5f02\u8d28\u6027\u7684\u80bf\u7624\u3002\u5404\u5206\u5b50\u5206\u578b\u95f4\u53d1\u75c5\u5e74\u9f84\u3001\u4e34\u5e8a\u7279\u5f81\u3001\u6076\u6027\u7a0b\u5ea6\u53ca\u9884\u540e\u7b49\u65b9\u9762\u5404\u4e0d\u76f8\u540c\u3002\u901a\u8fc7\u5bf9\u4e73\u817a\u764c\u8fdb\u884c\u5206\u5b50\u5206\u578b\uff0c\u671f\u671b\u8fdb\u4e00\u6b65\u5224\u65ad\u5176\u751f\u7269\u5b66\u884c\u4e3a\uff0c\u6307\u5bfc\u5236\u5b9a\u66f4\u5177\u6709\u9488\u5bf9\u6027\u7684\u6cbb\u7597\u65b9\u6848\uff0c\u4f7f\u6bcf\u4f4d\u60a3\u8005\u83b7\u5f97\u6700\u4f73\u7684\u6cbb\u7597\uff0c\u771f\u6b63\u505a\u5230<\/span>\u201c\u91cf\u4f53\u88c1\u8863\u3001\u5bf9\u75c7\u4e0b\u836f<\/span>\u201d<\/span>\u3002<\/span><\/span><\/p>\n


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

2000\u5e74\uff0c<\/span>Perou<\/span>\u7b49\u9996\u5148\u63d0\u51fa\u4e86\u4e73\u817a\u764c\u7684\u5206\u5b50\u5206\u578b\u6982\u5ff5\uff0c\u76ee\u524d\u516c\u8ba4\u7684\u5206\u578b\u662f\u6839\u636e<\/span>ER<\/span>\u3001<\/span>PR<\/span>\u3001<\/span>HER-2<\/span>\u3001\u7ec6\u80de\u589e\u6b96\u6307\u6570<\/span>Ki-67<\/span>\u7684\u57fa\u56e0\u8868\u8fbe\u60c5\u51b5\u628a\u4e73\u817a\u764c\u5206\u4e3a<\/span>Luminal A<\/span>\u4e0e<\/span>Luminal B<\/span>\u4e73\u817a\u764c\u3001<\/span>HER-2<\/span>\u9633\u6027\u4e73\u817a\u764c\u3001\u4e09\u9634\u6027\u4e73\u817a\u764c<\/span><\/span>[<\/span><\/sup>3<\/span><\/sup>]<\/span><\/sup>\u3002\u5206\u5b50\u5206\u578b\u5982\u4e0b\u56fe\u6240\u793a\uff1a<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

\u4e73\u817a\u764c\u5c5e\u6fc0\u7d20\u4f9d\u8d56\u6027\u80bf\u7624\uff0c<\/span>\u5176\u4e2d\u6fc0\u7d20\u53d7\u4f53\u9633\u6027\u578b\uff08<\/span>HR+\uff09\u4e73\u817a\u764c\u662f\u6307\u96cc\u6fc0\u7d20\u53d7\u4f53\uff08<\/span>ER<\/span>\uff09\u548c\u6216\u5b55\u6fc0\u7d20\u53d7\u4f53\uff08<\/span>PR<\/span>\uff09\u8868\u8fbe\u9633\u6027\u7684\u60a3\u8005\uff0c\u7ea6\u5360\u6240\u6709\u4e73\u817a\u764c\u7c7b\u578b\u7684<\/span>75%<\/span><\/strong>\u3002<\/span>\u5185\u5206\u6ccc\u6cbb\u7597\u662f\u8fd9\u7c7b\u4e73\u817a\u764c\u7684\u6709\u6548\u6cbb\u7597\u65b9\u5f0f\u4e4b\u4e00<\/span><\/strong>\uff0c<\/span>CDK4\/6\u6291\u5236\u5242\u662f\u5189\u5189\u5347\u8d77\u7684\u6297\u764c<\/span>\u201c<\/span>\u795e\u836f<\/span>\u201d<\/span>\uff0c\u6b63\u5728\u8fc5\u901f\u6539\u53d8\u6fc0\u7d20\u53d7\u4f53\uff08<\/span>HR<\/span>\uff09\u9633\u6027\uff0c\u4eba\u8868\u76ae\u751f\u957f\u56e0\u5b50\u53d7\u4f53<\/span>2<\/span>\uff08<\/span>HER2<\/span>\uff09\u9634\u6027\u548c\uff08<\/span>HR + HER2-<\/span>\uff09\u665a\u671f\u4e73\u817a\u764c\u7684\u6cbb\u7597\u683c\u5c40\uff0c\u6709\u6548\u5730\u514b\u670d\u6216\u5ef6\u8fdf\u5185\u5206\u6ccc\u62b5\u6297\u7684\u51fa\u73b0\uff0c\u4e3a\u665a\u671f\u60a3\u8005\u4e89\u53d6\u66f4\u591a\u7684\u751f\u5b58\u65f6\u95f4\u3002<\/span><\/span><\/span>\u57fa\u7840\u7814\u7a76<\/span>\u4e5f\u5f00\u59cb\u9526\u4e0a\u6dfb\u82b1\uff0c\u6700\u8fd1\u6709\u7814\u7a76\u663e\u793a<\/span>CDK4\/6\u6291\u5236\u5242\u4e0d\u4ec5\u76f4\u63a5\u6740\u4f24<\/span><\/span>\u80bf\u7624<\/span>\u7ec6\u80de\uff0c\u8fd8\u6fc0\u6d3b\u514d\u75ab\u7cfb\u7edf\u3001\u548c\u514d\u75ab\u7597\u6cd5\u6709\u4e00\u5b9a\u5173\u8054\u3002\u7ec6\u80de\u5468\u671f\u86cb\u767d\u4f9d\u8d56\u6027\u6fc0\u9176<\/span>4\u548c<\/span>6<\/span>\uff08<\/span>CDK4\/6<\/span>\uff09\u6291\u5236\u5242\u7684\u5f15\u5165\u663e\u7740\u6539\u5584\u4e86\u665a\u671f\u4e73\u817a\u764c\u5973\u6027\u7684\u9884\u540e\u3002<\/span><\/span><\/p>\n


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CDK<\/span><\/strong>4\/6<\/span><\/strong>\u6291\u5236\u5242\u7684\u4f5c\u7528\u673a\u5236<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n

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\u5468\u671f\u86cb\u767d\u4f9d\u8d56\u6027\u6fc0\u9176\uff08<\/span>CDK\uff09<\/span>4\/6 <\/span>\u662f\u7ec6\u80de\u5468\u671f\u7684\u5173\u952e\u8c03\u8282\u56e0\u5b50\uff0c\u901a\u8fc7\u4e0e<\/span>cyclin D<\/span>\u5f62\u6210\u590d\u5408\u7269\uff0c\u78f7\u9178\u5316<\/span>Rb<\/span>\uff0c\u91ca\u653e<\/span>E2F<\/span>\uff0c\u4ece\u800c\u80fd\u591f\u89e6\u53d1\u7ec6\u80de\u5468\u671f\u4ece<\/span>DNA<\/span>\u5408\u6210\u524d\u671f\uff08<\/span>G1<\/span>\u671f\uff09\u8fdb\u5165\u5230 <\/span>DNA <\/span>\u590d\u5236\u671f\uff08<\/span>S1<\/span>\u671f\uff09\u3002\u5728<\/span>ER+<\/span>\u4e73\u817a\u764c\u4e2d\uff0c<\/span>CDK4\/6-cyclinD-Rb<\/span>\u901a\u8def\u975e\u5e38\u91cd\u8981\uff0c\u4e14\u662f<\/span>ER<\/span>\u4fe1\u53f7\u7684\u5173\u952e\u4e0b\u6e38\u9776\u6807\u3002\u56e0\u6b64\uff0c\u963b\u65ad\u4e86<\/span>CDK4\/6<\/span>\u6fc0\u9176\u7684\u6d3b\u6027\uff0c\u6062\u590d\u7ec6\u80de\u5468\u671f\u63a7\u5236\uff0c\u963b\u65ad\u80bf\u7624\u7ec6\u80de\u589e\u6b96\uff0c\u4e5f\u5c31\u6291\u5236\u4e86\u4e73\u817a\u764c\u7ec6\u80de\u7684\u751f\u957f\u3002\u56e0\u6b64\uff0c\u5bf9\u5176\u5e72\u9884\u6210\u4e3a\u4e00\u79cd\u6cbb\u7597\u7b56\u7565\uff0c<\/span>CDK4\/6\u4e5f\u56e0\u6b64\u6210\u4e3a\u6297\u80bf\u7624\u7684\u9776\u70b9\u4e4b\u4e00\u3002<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

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\u8fd1<\/span>10\u5e74\u6765\u665a\u671f\u4e73\u817a\u764c\u7684\u6cbb\u7597\u65e0\u91cd\u5927\u8fdb\u5c55\uff0c\u7f3a\u4e4f\u7a81\u7834\u6027\u521b\u65b0\u7597\u6cd5\u3002\u665a\u671f\u4e73\u817a\u764c\u60a3\u8005\u7684\u603b\u4f53\u4e2d\u4f4d\u751f\u5b58\u671f\u4ec5\u6709<\/span>2-3<\/span>\u5e74\uff0c<\/span>5<\/span>\u5e74\u751f\u5b58\u7387\u4ec5\u7ea6<\/span>20%<\/span>\uff0c\u8feb\u5207\u9700\u8981\u521b\u65b0\u6cbb\u7597\u65b9\u6848\uff0c<\/span> <\/span>Palbociclib<\/span><\/strong>\u4f5c\u4e3a\u5168\u7403\u9996\u4e2a<\/span>CDK4\/6\u6291\u5236\u5242\u4e5f\u662f\u56fd\u5185\u9996\u4e2a\u4e0a\u5e02\u7684<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\uff0c\u6b63\u5f0f\u5f00\u542f\u4e86<\/span>HR<\/span>\u9633\u6027\u665a\u671f\u4e73\u817a\u764c\u9776\u5411\u6cbb\u7597\u7684\u65b0\u65f6\u4ee3<\/span><\/strong>\u3002<\/span>Palbociclib\u836f\u7269\u963b\u65ad\u4e86<\/span>CDK 4<\/span>\u548c<\/span>CDK 6<\/span>\u86cb\u767d\u7684\u529f\u80fd\uff0c\u8fd9\u4e24\u79cd\u86cb\u767d\u90fd\u80fd\u4fc3\u8fdb\u7ec6\u80de\u589e\u6b96\uff0c\u4fc3\u8fdb<\/span><\/span><\/span>\u80bf\u7624<\/span>\u7684\u751f\u957f\u3002\u8fd9\u4e9b\u836f\u7269\u4e0e\u82b3\u9999\u5316\u9176\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\uff0c\u4f5c\u4e3a\u7edd\u7ecf\u540e\u6fc0\u7d20\u53d7\u4f53\u9633\u6027\u3001<\/span>HER-2\u9634\u6027\u7684\u665a\u671f\u6216\u8f6c\u79fb\u6027\u75be\u75c5\u7684\u521d\u59cb\u5185\u5206\u6ccc\u6cbb\u7597\u3002<\/span><\/span>CDK4\/6\u6291\u5236\u5242<\/span><\/span><\/strong>\u53ef\u4ee5\u8bf4\u662f\u4e73\u817a\u764c\u6cbb\u7597\u9886\u57df\u7684\u91cd\u78c5\u836f\u7269\u3002\u8fd9\u4e2a\u836f\u7684\u4f7f\u7528\u5728\u4e0d\u65ad\u7684\u6269\u5927\uff0c\u7597\u6548\u60ca\u4eba\uff0c\u526f\u4f5c\u7528\u4e5f\u5728\u53ef\u63a7\u8303\u56f4\u4e4b\u5185\uff0c\u800c\u4e14\u5b83\u7684\u9002\u5e94\u75c7\u76ee\u524d\u8fd8\u5728\u4e0d\u65ad\u6269\u5bbd\uff0c\u6240\u4ee5\u5404\u5927\u516c\u53f8\u90fd\u56f4\u7ed5\u7740<\/span>CDK4\/6\u6291\u5236\u5242\u5c55\u5f00\u4e86\u5bc6\u5207\u7684\u7814\u7a76\u3002<\/span><\/span> \u672c\u6587\u4e3b\u8981\u5bf9<\/span>CDK4\/6\u4e3a\u9776\u70b9\u7684\u4e73\u817a\u764c\u9776\u5411\u6cbb\u7597\u7814\u7a76\u8fdb\u884c\u7efc\u8ff0\u3002<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

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1. <\/span>\u5e15\u535a\u897f\u5c3c\uff08<\/span><\/strong>palbociclib<\/span><\/strong>\uff09<\/span><\/strong><\/h1>\n<\/section>\n
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<\/section>\n<\/section>\n<\/section>\n

\u5e15\u535a\u897f\u5c3c\u4e00\u79cd\u5b9e\u9a8c\u6027\u3001\u53e3\u670d\u3001\u9776\u5411\u6027<\/span> CDK4\/6 \u6291\u5236\u5242\uff0c\u80fd\u591f\u9009\u62e9\u6027\u6291\u5236\u7ec6\u80de\u5468\u671f\u86cb\u767d\u4f9d\u8d56\u6027\u6fc0\u9176<\/span>4<\/span>\u548c<\/span>6<\/span>\uff08<\/span>CDK4\/6<\/span>\uff09 \uff0c\u6062\u590d\u7ec6\u80de\u5468\u671f\u63a7\u5236\uff0c\u963b\u65ad\u80bf\u7624\u7ec6\u80de\u589e\u6b96\u3002\u5728<\/span>2012<\/span>\u5e74\u5723\u5b89\u4e1c\u5c3c\u5965\u4e73\u817a\u764c\u4f1a\u8bae\u4e0a\uff08<\/span>SABCS<\/span>\uff09\uff0c\u4e00\u7ecf\u53d1\u5e03\u5c31\u5f15\u8d77\u884c\u4e1a\u5e7f\u6cdb\u5173\u6ce8\u3002<\/span>2013 <\/span>\u5e74 <\/span>4 <\/span>\u6708\u83b7 \u5f97 \u7f8e \u56fd <\/span>FDA <\/span>\u7684<\/span>” <\/span>\u7a81\u7834 \u6027 \u7597 \u6cd5 <\/span>“<\/span>\u8d44 \u683c\uff0c<\/span>2014<\/span>\u5e74<\/span>10<\/span>\u6708<\/span>13<\/span>\u65e5\uff0c\u8f89\u745e\u5ba3\u5e03<\/span>FDA<\/span>\u6388\u4e88\u8be5\u516c\u53f8<\/span>Palbociclib<\/span>\u4e0a\u5e02\u7533\u8bf7\u4f18\u5148\u5ba1\u8bc4\u8d44\u683c<\/span>\uff0c<\/span> <\/span>\u5e15\u535a\u897f\u5c3c\u8054\u5408\u6765\u66f2\u5511\u4e8e<\/span> 2015 \u5e74 <\/span>2 <\/span>\u6708\u83b7\u5f97\u52a0\u901f\u6279\u51c6\uff0c\u5e76\u4e8e <\/span>2016 <\/span>\u5e74 <\/span>2 <\/span>\u6708\u83b7\u5f97\u5e38\u89c4\u6279\u51c6\uff0c\u5176\u7b2c\u4e8c\u4e2a\u9002\u5e94\u75c7\u662f\uff1a\u4e0e\u6c1f\u7ef4\u53f8\u7fa4\u8054\u5408\u7528\u836f\uff0c\u7528\u4e8e\u63a5\u53d7\u5185\u5206\u6ccc\u6cbb\u7597\u4f46\u75c5\u60c5\u6076\u5316\u7684 <\/span>HR-<\/span>\u9633\u6027\u3001<\/span>HER2-<\/span>\u9634\u6027\u665a\u671f\u6216\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u60a3\u8005\u7684\u6cbb\u7597\u3002\u73b0\u4eca\uff0c\u5e15\u535a\u897f\u5c3c\u52a0\u6765\u66f2\u5511\u662f\u7ecf <\/span>FDA <\/span>\u6279\u51c6\u7528\u4e8e <\/span>HR-<\/span>\u9633\u6027\u3001<\/span>HER2-<\/span>\u9634\u6027\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u7684\u9996\u9009\u53e3\u670d\u8054\u5408\u6cbb\u7597\u3002<\/span><\/span><\/p>\n


<\/span><\/strong><\/h1>\n

\u57fa\u672c\u4fe1\u606f<\/span><\/strong><\/span><\/o:p><\/span><\/strong><\/h1>\n


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\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


<\/span><\/strong><\/span><\/p>\n

\u4e34\u5e8a\u8bd5\u9a8c<\/span><\/strong><\/span><\/p>\n

 <\/span><\/p>\n

Palbociclib\u662f<\/span>FDA<\/span>\u6279\u51c6\u7684\u9996\u4e2a<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\uff0c\u8be5\u836f\u5728\u4e73\u817a\u764c\u5f00\u5c55<\/span>PALOMA1\/2\/3<\/span>\u4e00\u7cfb\u5217\u4e34\u5e8a\u7814\u7a76[<\/span>4,5]\u3002\u57fa\u4e8e<\/span>II\u671f\u7814\u7a76<\/span>PALOMA-1<\/span>\uff0c<\/span>2015<\/span>\u5e74<\/span>2<\/span>\u6708<\/span>3<\/span>\u65e5<\/span>FDA<\/span>\u52a0\u901f\u6279\u51c6\u4e86<\/span>palbociclib<\/span>\u8054\u5408\u6765\u66f2\u5511\u7528\u4e8e\u7edd\u7ecf\u540e <\/span>ER+\/HER2-<\/span>\u665a\u671f\u4e73\u817a\u764c\u7684\u4e00\u7ebf\u6cbb\u7597\u3002<\/span>2016<\/span>\u5e74<\/span>2<\/span>\u6708<\/span>19<\/span>\u65e5<\/span>FDA<\/span>\u6839\u636e<\/span>III<\/span>\u671f<\/span>PALOMA-3<\/span>\u7814\u7a76\u6279\u51c6\u4e86<\/span>IBRANCE<\/span>\u8054\u5408\u6c1f\u7ef4\u53f8\u7fa4\u7528\u4e8e\u65e2\u5f80\u5185\u5206\u6ccc\u6cbb\u7597\u5931\u8d25\u7684<\/span>HR+\/HER2- <\/span>\u7edd\u7ecf\u540e\u665a\u671f\u4e73\u817a\u764c\u3002<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

<\/span>
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\u7531\u8868\u683c\u4e2d\u7684<\/span>PFS<\/span>\u53ef\u4ee5\u770b\u5230\uff0c\u5bf9\u4e8e<\/span>ER<\/span>\u3001<\/span>PR+<\/span>\u7684\u4e73\u817a\u764c\u60a3\u8005\uff0c\u53ef\u4ee5\u5728<\/span><\/p>\n

\uff08<\/span>1\uff09\u4f20\u7edf\u5185\u5206\u6ccc\u836f\u7269\u5982\u6765\u66f2\u5511\u3001\u4ed6\u83ab\u6614\u82ac\u8010\u836f\u540e\u52a0\u4e0a<\/span>Ibrance<\/span>\u4f7f\u7528\uff0c\u6bd4\u65e2\u5f80\u4e8c\u7ebf\u65b9\u6848\u6c1f\u7ef4\u53f8\u7fa4<\/span>PFS<\/span>\u7ffb\u500d\uff1b\uff08<\/span>2<\/span>\uff09\u5982\u679c\u7ecf\u6d4e\u53ef\u4ee5\uff0c\u60a3\u8005\u53ef\u4ee5\u76f4\u63a5\u5728\u5185\u5206\u6ccc\u521d\u6cbb\u65f6\u5c31\u76f4\u63a5\u91c7\u7528<\/span>Ibrance+<\/span>\u5185\u5206\u6ccc\u836f\u7269\uff0c\u53ef\u83b7\u5f97<\/span>PFS 24.8<\/span>\u4e2a\u6708\u7684\u65e0\u8fdb\u5c55\u671f\u3002\u65e0\u8bba\u5185\u5206\u6ccc\u4e00\u7ebf\u4e8c\u7ebf\uff0c\u90fd\u5c06\u5185\u5206\u6ccc\u836f\u7269\u7684\u7ef4\u6301\u65f6\u95f4\u660e\u663e\u5ef6\u957f\uff0c\u6b64\u836f\u7684\u56fd\u5185\u4e0a\u5e02\u786e\u5b9e\u4e3a\u5185\u5206\u6ccc\u578b\u4e73\u817a\u764c\u60a3\u8005\u5e26\u6765\u65b0\u7684\u6cbb\u7597\u5e0c\u671b\u3002<\/span><\/span><\/p>\n


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

\u56fd\u5185\u7533\u62a5\u60c5\u51b5<\/span><\/strong><\/span><\/o:p><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

\u4ee5\u4e0a\u6570\u636e\u6765\u6e90\u4e8e\u836f\u667a\u7f51<\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u53d4\u4e01\u57fa\u6c27\u7fb0\u57fa\u4fdd\u62a4\u7684\u54cc\u55ea\u548c<\/span> 5-\u6eb4<\/span>-2-<\/span>\u785d\u57fa\u5421\u5576\u5728\u6c2e\u6c14\u4fdd\u62a4\u4e0b\u4e8e <\/span>65<\/span>\uff5e<\/span>70 \u2103<\/span>\u4e0b\u53cd\u5e94 <\/span>30 h<\/span>\uff0c\u540e\u5904\u7406\u5f97\u5230\u5316\u5408\u7269 <\/span>1<\/span>\uff0c\u5316\u5408\u7269 <\/span>1 <\/span>\u5728 <\/span>Pd\/C <\/span>\u50ac\u5316\u4e0b\uff0c\u6c22\u6c14\u8fd8\u539f\u5f97\u5230\u5316\u5408\u7269 <\/span>2<\/span>\u3002<\/span>5-<\/span>\u6eb4<\/span>-2,4-<\/span>\u4e8c\u6c2f\u5627\u5576\u548c\u73af\u620a\u80fa\u5728 <\/span>25 \u2103<\/span>\u4e0b\u53cd\u5e94 <\/span>2 h <\/span>\u5f97\u5230\u5316\u5408\u7269 <\/span>3<\/span>\u3002\u5316\u5408\u7269 <\/span>3 <\/span>\u548c\u4e01\u70ef\u9178\u5728 <\/span>THF<\/span>\u548c\u4e8c\u5f02\u4e19\u57fa\u4e59\u57fa\u80fa\u4e2d\u6df7\u5408\u6405\u62cc\uff0c\u7136\u540e\u52a0\u5165\u4e09\u90bb\u7532\u82ef\u57fa\u78f7<\/span>[(o-Tol)3P]<\/span>\u548c\u53cd\u4e8c\u8148\u82ef\u4e8c\u6c2f\u5316\u94af<\/span>[Pd Cl2(Ph CN)2]<\/span>\uff0c\u4e0a\u8ff0\u6df7\u5408\u7269\u5728 <\/span>70 \u2103<\/span>\u4e0b\u53cd\u5e94 <\/span>16 h<\/span>\uff0c\u7136\u540e\u52a0\u5165\u4e59\u9178\u9150\uff0c\u7ee7\u7eed\u6405\u62cc<\/span>1.5 h<\/span>\uff0c\u7ecf\u8fc7\u540e\u5904\u7406\u5f97\u5230\u5316\u5408\u7269 <\/span>4<\/span>\u3002\u5316\u5408\u7269<\/span>4 <\/span>\u548c\u6eb4\u3001\u918b\u9178\u94a0\u5728\u51b0\u918b\u9178\u4e2d\u6df7\u5408\uff0c\u6eb6\u6db2\u52a0\u70ed\u5230 <\/span>50 \u2103<\/span>\u5e76\u6405\u62cc <\/span>35 h<\/span>\uff0c\u5f97\u5230\u5316\u5408\u7269 <\/span>5<\/span>\u3002\u5316\u5408\u7269 <\/span>2 <\/span>\u548c\u4e8c<\/span>(<\/span>\u4e09\u7532\u57fa\u7845\u57fa<\/span>)<\/span>\u6c28\u57fa\u9502\u5728 <\/span>THF <\/span>\u4e2d\u6df7\u5408\u6405\u62cc <\/span>10 min <\/span>\u540e\u52a0\u5165\u5316\u5408\u7269 <\/span>5<\/span>\uff0c\u7ee7\u7eed\u53cd\u5e94 <\/span>30 min <\/span>\u540e\u5f97\u5230\u5316\u5408\u7269 <\/span>6<\/span>\u3002\u5316\u5408\u7269 <\/span>6<\/span>\u548c\u4e01\u57fa\u4e59\u70ef\u57fa\u919a\u5728\u6b63\u4e01\u9187\u548c\u4e8c\u5f02\u4e19\u57fa\u4e59\u57fa\u80fa\u4e2d\u6df7\u5408\u6405\u62cc\uff0c\u7136\u540e\u52a0\u5165<\/span>[1,1′-<\/span>\u53cc<\/span>(<\/span>\u4e8c\u82ef\u57fa\u81a6<\/span>)<\/span>\u4e8c\u8302\u94c1<\/span>]<\/span>\u4e8c\u6c2f\u5316\u94af\u4e8c\u6c2f\u7532\u70f7\u7edc\u5408\u7269<\/span>[Pd(dppf)2Cl2]<\/span>\uff0c\u4e0a\u8ff0\u6df7\u5408\u7269\u5728 <\/span>95 \u2103<\/span>\u4e0b\u53cd\u5e94 <\/span>20 h<\/span>\uff0c\u7136\u540e\u7ecf\u8fc7\u540e\u5904\u7406\u5f97\u5230\u5316\u5408\u7269 <\/span>7<\/span>\u3002\u5316\u5408\u7269 <\/span>7 <\/span>\u548c\u7532\u9187\u6df7\u5408\u52a0\u70ed\u81f3 <\/span>55<\/span>\uff5e<\/span>60 \u2103<\/span>\uff0c\u52a0\u5165\u7f9f\u4e59\u78fa\u9178\u540e\u5904\u7406\u5f97\u5230\u76ee\u6807\u5316\u5408\u7269 <\/span>palbociclib <\/span>\u7684\u7f9f\u4e59\u78fa\u9178\u76d0\u3002<\/span>palbociclib <\/span>\u7684\u5408\u6210\u8def\u7ebf\u89c1\u56fe<\/span>[6]<\/span><\/sup>\uff1a<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

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

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2. <\/span>\u745e\u535a\u897f\u5c3c<\/span><\/strong>(ribociclib)<\/span><\/strong><\/p>\n<\/section>\n

<\/section>\n
<\/section>\n<\/section>\n<\/section>\n

\u745e\u535a\u897f\u5c3c<\/span>(ribociclib)\u7531\u745e\u58eb\u8bfa\u534e\u5236\u836f\u6709\u9650\u516c\u53f8\u7814\u5236\uff0c\u662f\u4e00\u79cd\u7ec6\u80de\u5468\u671f\u86cb\u767d\u4f9d\u8d56\u6027\u6fc0\u9176<\/span>4\/6(CDK4\/6)<\/span>\u6291\u5236\u836f\uff0c\u7528\u4e8e\u6cbb\u7597\u6fc0\u7d20\u53d7\u4f53\u9633\u6027\u3001\u4eba\u8868\u76ae\u751f\u957f\u56e0\u5b50\u53d7\u4f53<\/span>-2<\/span>\u9634\u6027<\/span>(HR<\/span><\/span>+<\/span><\/sup>\/HER2<\/span>–<\/span><\/sup>)\u7684\u7edd\u7ecf\u540e\u5987\u5973\u665a\u671f\u6216\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u3002<\/span>2016<\/span>\u5e74<\/span>8<\/span>\u6708<\/span>9<\/span>\u65e5\u83b7\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u7ba1\u7406\u5c40<\/span>(FDA)<\/span>\u7a81\u7834\u6027\u7597\u6cd5\u8d44\u683c\u3002<\/span>FDA<\/span>\u4e8e<\/span>2016<\/span>\u5e74<\/span>11<\/span>\u6708<\/span>9<\/span>\u65e5\u63a5\u53d7\u8bfa\u534e\u5236\u836f\u6709\u9650\u516c\u53f8\u745e\u535a\u897f\u5c3c\u7684\u65b0\u836f\u4e0a\u5e02\u7533\u8bf7\uff0c\u4f5c\u4e3a\u4e00\u7ebf\u6cbb\u7597\u836f\u7269<\/span><\/span>\uff0c<\/span>\u4e0e\u6765\u66f2\u5511\u7ec4\u5408\u7528\u836f\u3002<\/span>FDA\u7ed9\u4e88\u4f18\u5148\u5ba1\u67e5\u8d44\u683c\uff0c\u4e8e<\/span>2017<\/span>\u5e74<\/span>3<\/span>\u6708<\/span>17<\/span>\u65e5\u6b63\u5f0f\u6279\u51c6\u4e0a\u5e02\uff0c\u5546\u54c1\u540d\u4e3a<\/span>Kisqali<\/span>\u3002<\/span><\/span><\/o:p><\/span><\/span><\/p>\n


<\/span><\/strong><\/p>\n

\u57fa\u672c\u4fe1\u606f<\/span><\/strong><\/span><\/o:p><\/span><\/strong><\/p>\n


<\/span><\/strong><\/span><\/p>\n

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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


<\/span><\/strong><\/span><\/p>\n

\u4e34\u5e8a\u8bd5\u9a8c<\/span><\/strong><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

Kisqali\u7684\u83b7\u6279\u4e3b\u8981\u662f\u57fa\u4e8e\u4e34\u5e8a\u8bd5\u9a8c<\/span>MONALEESA-2<\/span>\u7684\u826f\u597d\u8bd5\u9a8c\u7ed3\u679c\u3002<\/span> MONALEESA-2\u662f\u4e00\u9879\u968f\u673a\u53cc\u76f2\uff0c\u5b89\u6170\u5242\u5bf9\u7167\u7684\u4e09\u671f\u56fd\u9645\u4e34\u5e8a\u7814\u7a76\uff0c<\/span><\/span>\u7814\u7a76<\/span>1(MONALEESA-2)<\/span>\u662f\u5728\u6709<\/span>HR-<\/span>\u9633\u6027\uff0c<\/span>HER2-<\/span>\u9634\u6027\uff0c\u665a\u671f\u4e73\u764c\u60a3\u8005\u5bf9\u665a\u671f\u75be\u75c5\u672a\u63a5\u53d7\u4ee5\u524d\u6cbb\u7597\u7edd\u7ecf\u540e\u5987\u5973\u8fdb\u884c<\/span>KISQALI<\/span>\u52a0\u6765\u66f2\u5511\u76f8\u6bd4\u8f83\u5b89\u6170\u5242\u52a0\u6765\u66f2\u5511\u4e00\u9879\u968f\u673a\u5316\uff0c\u53cc\u76f2\uff0c\u5b89\u6170\u5242<\/span>–<\/span>\u5bf9\u7167\uff0c\u591a\u4e2d\u5fc3\u4e34\u5e8a\u7814\u7a76\u3002<\/span><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

Ap-\u503c\u4ece\u5355\u4fa7\u65f6\u5e8f\u68c0\u9a8c\u6cd5<\/span>[log-rank test]<\/span>\u4f30\u7b97\u3002<\/span>NR=<\/span>\u672a\u8fbe\u5230<\/span><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u5627\u5576\u5316\u5408\u7269<\/span> 5-\u6eb4<\/span>-2,4-<\/span>\u4e8c\u6c2f\u5627\u5576\u548c\u73af\u620a\u80fa\u7ecf\u82b3\u9999\u4eb2\u6838\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269 <\/span>1<\/span>\uff0c\u901a\u8fc7 <\/span>Sonogashira <\/span>\u5076\u8054\u53cd\u5e94\uff0c\u5f97\u5230\u5316\u5408\u7269 <\/span>2<\/span>\uff0c\u968f\u540e\u5728\u78b1\u6027\u6761\u4ef6\u4e0b\u73af\u5316\uff0c\u5f97\u5230\u5316\u5408\u7269 <\/span>3<\/span>\u3002\u5316\u5408\u7269 <\/span>3 <\/span>\u5728 <\/span>MnO 2 <\/span>\u4ee5\u53ca <\/span>NaCN <\/span>\u7684\u6761\u4ef6\u4e0b\u7ecf\u8fc7\u4e2d\u95f4\u4f53\uff0c\u4e0e\u4e8c\u7532\u80fa\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269 <\/span>4<\/span>\u3002\u54cc\u55ea\u548c <\/span>2-<\/span>\u785d\u57fa<\/span>-5-<\/span>\u6c2f\u5421\u5576\u7ecf\u8fc7\u82b3\u9999\u4eb2\u6838\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269 <\/span>5<\/span>\uff0c\u968f\u540e <\/span>Boc <\/span>\u4fdd\u62a4\u6c28\u57fa\uff0c\u6c22\u5316\u8fd8\u539f\u785d\u57fa\u5f97\u5230\u5316\u5408\u7269 <\/span>6<\/span>\u3002\u5c06\u5316\u5408\u7269 <\/span>4 <\/span>\u548c\u5316\u5408\u7269 <\/span>6 <\/span>\u901a\u8fc7 <\/span>Buchwald\u2013Hartwig <\/span>\u80fa\u5316\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269 <\/span>7<\/span>\uff0c\u5728 <\/span>HCl <\/span>\u5b58\u5728\u4e0b\u8131\u9664<\/span>Boc <\/span>\u4fdd\u62a4\u57fa\uff0c\u5f97\u5230\u5316\u5408\u7269 <\/span>8<\/span>\uff0c\u5c06\u5176\u8f6c\u5316\u4e3a\u7425\u73c0\u9178\u76d0\u5373\u5f97\u5230\u76ee\u6807\u5316\u5408\u7269 <\/span>ribociclib<\/span>[8,9]\u3002<\/span><\/span><\/p>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n

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

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<\/section>\n
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3.<\/span><\/strong>Verzenio\uff08<\/span>abemaciclib<\/span>\uff09<\/span><\/span><\/strong><\/p>\n<\/section>\n

<\/section>\n
<\/section>\n<\/section>\n<\/section>\n

2017\u5e74<\/span>9<\/span>\u6708<\/span>28<\/span>\u65e5\uff0c<\/span>FDA\u6279\u51c6<\/span>abemaciclib<\/span>\uff08<\/span>VERZENIO\u2122<\/span>\uff0c\u793c\u6765\uff09\u6210\u4e3a\u7b2c\u4e00\u4e2a\u4e5f\u662f\u552f\u4e00\u83b7\u5f97\u6279\u51c6\u7684\u53ef\u4ee5\u8054\u5408\u4ee5\u53ca\u5355\u836f\u7528\u4e8e\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u6cbb\u7597\u7684\u7ec6\u80de\u5468\u671f\u86cb\u767d\u4f9d\u8d56\u6fc0\u9176<\/span>(CDK)4\/6<\/span>\u6291\u5236\u5242\uff0c<\/span><\/strong>\u5355\u4e00\u7597\u6cd5\u7528\u4e8e\u7ecf\u6cbb\u7684<\/span>HR+\/HER2\u665a\u671f\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u6210\u5e74\u60a3\u8005\u5316\u7597\u524d\u7684\u4e8c\u7ebf\u5185\u5206\u6ccc\u6cbb\u7597\uff0c\u540c\u65f6\u4e5f\u6279\u51c6<\/span>abemaciclib<\/span>\u8054\u5408\u6c1f\u7ef4\u53f8\u7fa4\u7528\u4e8e\u7ecf\u6cbb\u7684<\/span>HR+\/HER2<\/span>\u665a\u671f\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u5973\u6027\u60a3\u8005\u7684\u4e8c\u7ebf\u5185\u5206\u6ccc\u7597\u6cd5\u3002<\/span>2018<\/span>\u5e74<\/span>2<\/span>\u6708<\/span>26<\/span>\u65e5\uff0c<\/span>FDA<\/span>\u6279\u51c6<\/span>abemaciclib<\/span>\u4e0e\u82b3\u9999\u5316\u9176\u6291\u5236\u5242\u8054\u5408\u5e94\u7528\u4e8e\u7edd\u7ecf\u540e\u6fc0\u7d20\u53d7\u4f53\uff08<\/span>HR<\/span>\uff09\u9633\u6027<\/span>HER2<\/span>\u9634\u6027\u665a\u671f\u6216\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u7684\u4e00\u7ebf\u5185\u5206\u6ccc\u6cbb\u7597\u3002<\/span><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u57fa\u672c\u4fe1\u606f<\/span><\/strong><\/span><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


<\/span><\/strong><\/p>\n

\u4e34\u5e8a\u8bd5\u9a8c<\/span><\/strong><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

abemaciclib\u7684\u5355\u836f\u6cbb\u7597\u6279\u51c6\u57fa\u4e8e\u7b2c\u4e8c\u9636\u6bb5<\/span><\/span>MONARCH1<\/span><\/strong>\u8bd5\u9a8c\u7684\u7ed3\u679c\uff0c\u8be5\u8bd5\u9a8c\u7eb3\u5165\u4e86<\/span>132\u4f8b<\/span>HR + \/ HER2-<\/span>\u8f6c\u79fb\u6027\u4e73\u817a\u764c\u60a3\u8005\uff0c\u8fd9\u4e9b\u60a3\u8005\u5728\u5185\u5206\u6ccc\u6cbb\u7597\u548c\u5316\u7597\u671f\u95f4\u6216\u4e4b\u540e\u8fdb\u5c55\u3002<\/span>  <\/span>\u7814\u7a76\u8005\u8bc4\u4f30\u7684<\/span>ORR<\/span>\u4e3a<\/span>19.7<\/span>\uff05\uff08<\/span>95<\/span>\uff05<\/span>CI<\/span>\uff0c<\/span>13.3<\/span>\uff05<\/span>-27.5<\/span>\uff05\uff09\uff0c\u4e2d\u4f4d\u53cd\u5e94\u6301\u7eed\u65f6\u95f4\u4e3a<\/span>8.6<\/span>\u4e2a\u6708\u3002<\/span> <\/span>\u72ec\u7acb\u8bc4\u4f30\u7684<\/span>ORR<\/span>\u4e3a<\/span>17.4<\/span>\uff05\uff08<\/span>95<\/span>\uff05<\/span>CI<\/span>\uff0c<\/span>11.4<\/span>\uff05<\/span>-25.0<\/span>\uff05\uff09\uff0c\u4e2d\u4f4d\u53cd\u5e94\u6301\u7eed\u65f6\u95f4\u4e3a<\/span>7.2<\/span>\u4e2a\u6708\u3002<\/span><\/span><\/span><\/p>\n

 <\/span><\/p>\n

abemaciclib\u548c\u6c1f\u7ef4\u53f8\u7fa4\u7684\u6279\u51c6\u662f\u57fa\u4e8e<\/span>III<\/span>\u671f<\/span><\/span>MONARCH2<\/span><\/strong>\u8bd5\u9a8c\u7684\u7ed3\u679c\uff0c\u8be5\u8bd5\u9a8c\u5c06\u60a3\u8005\u968f\u673a\u5206\u4e3a<\/span>abemaciclib\u52a0\u6c1f\u7ef4\u53f8\u7fa4\uff08<\/span>n = 446<\/span>\uff09\u6216\u6c1f\u7ef4\u53f8\u7fa4\u52a0\u5b89\u6170\u5242\uff08<\/span>n = 223<\/span>\uff09\u3002<\/span> <\/span>\u8be5\u7814\u7a76\u4e3b\u8981\u5305\u62ec\u7edd\u7ecf\u540e\u5987\u5973\uff08<\/span>82<\/span>\uff05\uff09\uff0c\u5176\u4f59\u4e3a\u7edd\u7ecf\u524d\u6216\u56f4\u7edd\u7ecf\u671f\u3002<\/span> abemaciclib<\/span>\u7ec4\u7684\u4e2d\u4f4d<\/span>PFS<\/span>\u4e3a<\/span>16.4<\/span>\u4e2a\u6708\uff08<\/span>95<\/span>\uff05<\/span>CI<\/span>\uff0c<\/span>14.4-19.3<\/span>\uff09\uff0c\u5355\u72ec\u6c1f\u7ef4\u53f8\u7fa4\u7ec4\u4e3a<\/span>9.3<\/span>\u4e2a\u6708\uff08<\/span>95<\/span>\uff05<\/span>CI<\/span>\uff0c<\/span>7.4-12.7<\/span>\uff09\uff08<\/span>HR<\/span>\uff0c<\/span>0.553; 95<\/span>\uff05<\/span>CI<\/span>\uff0c<\/span>0.449-0.681; P <.001<\/span>\uff09\u3002<\/span> <\/span>\u53ef\u6d4b\u91cf\u75be\u75c5\u60a3\u8005\u7684<\/span>ORR<\/span>\u5206\u522b\u4e3a<\/span>abemaciclib<\/span>\u548c\u5bf9\u7167\u7ec4\u7684<\/span>48.1<\/span>\uff05\u548c<\/span>21.3<\/span>\uff05\u3002<\/span> <\/span><\/span><\/span><\/p>\n


<\/span><\/strong><\/span><\/p>\n

MONARCH 3<\/span><\/strong>\u7814\u7a76\u4e2d\uff0c\u53e3\u670d<\/span>Verzenio 150\u6beb\u514b\uff0c\u6bcf\u65e5\u4e24\u6b21\uff0c\u8fde\u7eed\u7ed9\u836f\u5e76\u4e0e<\/span>AI <\/span>\u8054\u7528\u663e\u793a\u60a3\u8005\u65e0\u8fdb\u5c55\u751f\u5b58\u671f\u8d85\u8fc7<\/span>28<\/span>\u4e2a\u6708\uff08<\/span>28.2 <\/span>\u4e2a\u6708 <\/span>[95% CI: 23.5-NR]<\/span>\uff09\uff0c\u5b89\u6170\u5242\u8054\u5408<\/span>AI<\/span>\u7ec4\u4e3a<\/span>14.8<\/span>\u4e2a\u6708 <\/span>[95% CI: 11.2-19.2]<\/span>\uff0c<\/span>[HR: 0.54; 95% CI: 0.418-0.698, P < 0.0001]<\/span>\u3002\u5728\u53ef\u7528\u4e8e\u75be\u75c5\u8861\u91cf\u7684<\/span>Verzenio<\/span>\u8054\u7528<\/span>AI<\/span>\u60a3\u8005\u4e2d\uff08<\/span>N=267<\/span>\uff09\uff0c\u83b7\u5f97\u4e86<\/span>55.4%<\/span>\u7684\u5ba2\u89c2\u7f13\u89e3\u7387\uff08<\/span>ORR<\/span>\uff0c\u5b9a\u4e49\u4e3a\u5b8c\u5168\u7f13\u89e3\u52a0\u90e8\u5206\u7f13\u89e3\uff0c<\/span>CR + PR<\/span>\uff0c<\/span>PR<\/span>\u5b9a\u4e49\u4e3a\u9776\u75c5\u7076\u51cf\u5c11<\/span>\u226530%<\/span>\uff09<\/span>(n=148; 95% CI: 49.5-61.4)<\/span>\uff1b\u5ba2\u89c2\u7f13\u89e3\u7387\u4e3a<\/span>52.1%<\/span>\uff08<\/span>n=139<\/span>\uff09\uff0c\u5b8c\u5168\u7f13\u89e3\u7387\u4e3a<\/span>3.4%<\/span>\uff08<\/span>n=9<\/span>\uff09\u3002\u4e0e\u4e4b\u76f8\u6bd4\uff0c\u5b89\u6170\u5242<\/span>+AI<\/span>\u7ec4\u4e2d\u53ef\u6d4b\u91cf\u7684<\/span>132<\/span>\u540d\u60a3\u8005\u4e2d\uff0c<\/span>ORR<\/span>\u4e3a<\/span>40.2%<\/span>\uff08<\/span>n=53; 95% CI: 31.8-48.5<\/span>\uff09\uff0c\u5747\u4e3a\u90e8\u5206\u7f13\u89e3\u3002<\/span>Verzenio + AI<\/span>\u4e2d\u4f4d\u7f13\u89e3\u65f6\u95f4\u4e3a<\/span>27.4<\/span>\u4e2a\u6708\uff08<\/span>95% CI: 25.7-NR<\/span>\uff09\uff0c\u5b89\u6170\u5242<\/span>+AI<\/span>\u4e2d\u4f4d\u7f13\u89e3\u65f6\u95f4\u4e3a<\/span>17.5<\/span>\u4e2a\u6708\uff08<\/span>95% CI: 11.2-22.2<\/span>\uff09\u3002<\/span><\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/span><\/h1>\n

 <\/span><\/strong><\/h1>\n

\u9170\u80fa\u5316\u5408\u7269<\/span>S-2\u5728<\/span>POCl3<\/span>\u7684\u4f5c\u7528\u4e0b\uff0c\u5f62\u6210\u6c2f\u4e9a\u80fa\u4e2d\u95f4\u4f53\u63a5\u53d7\u82ef\u80fa\u5316\u5408\u7269<\/span>S-1<\/span>\u7684\u8fdb\u653b\u5f97\u5230\u5316\u5408\u7269<\/span>S-3<\/span>\uff0c<\/span>S-3<\/span>\u5728\u78b1\u6027\u6761\u4ef6\u4e0b\uff0c\u62d4\u53bb\u8d28\u5b50\uff0c\u7ecf\u8fc7\u4eb2\u6838\u82b3\u9999\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230\u82ef\u5e76\u54aa\u5511\u5316\u5408\u7269<\/span>S-4<\/span>\uff0c\u968f\u540e<\/span>S-4<\/span>\u82b3\u57fa\u6eb4\u901a\u8fc7<\/span>Pd<\/span>\u50ac\u5316\u548c<\/span>B2Pin2<\/span>\u53cd\u5e94\uff0c\u5236\u5907\u5f97\u5230\u82b3\u57fa\u7247\u90a3\u9187\u8102<\/span>S-5<\/span>\uff0c\u968f\u540e\u548c\u6c2f\u4ee3\u5627\u5576\u5316\u5408\u7269\u7ecf\u8fc7\u94af\u50ac\u5316\u7684<\/span>Suzuki<\/span>\u53cd\u5e94\u5f97\u5230\u5076\u8054\u4ea7\u7269<\/span>S-7<\/span>\u5f85\u7528\u3002\u4ef2\u80fa\u5316\u5408\u7269<\/span>S-8<\/span>\u548c\u919b<\/span>S-9<\/span>\u7ecf\u8fc7\u7f29\u5408\uff0c\u8fd8\u539f\u5f97\u5230\u80fa\u7c7b\u5316\u5408\u7269<\/span>S-10<\/span>\uff0c\u968f\u540e<\/span>S-10<\/span>\u5728<\/span>Pd<\/span>\u50ac\u5316\u4e0b\uff0c\u4ee5\u8054\u82ef\u578b<\/span>CyJohnPhos(<\/span>\u7ed3\u6784\u89c1\u540e\u6587<\/span>)<\/span>\u4f5c\u4e3a\u5927\u4f4d\u963b\u914d\u4f53\u4ee5\u53ca<\/span>LiHMDS<\/span>\u4f5c\u4e3a\u6c2e\u6e90\u5236\u5907<\/span>2-<\/span>\u6c28\u57fa\u5421\u5576\u5316\u5408\u7269<\/span>S-11<\/span>\u3002\u5f97\u5230<\/span>S-11<\/span>\u4ee5\u540e\uff0c\u5176\u548c<\/span>S-7<\/span>\u901a\u8fc7<\/span>Buchwald\u2013Hartwig<\/span>\u53cd\u5e94\uff0c\u5f97\u5230\u5316\u5408\u7269<\/span>S-12<\/span>\uff0c\u5c06\u5316\u5408\u7269<\/span>S-12<\/span>\u505a\u6210\u7532\u78fa\u9178\u76d0\u53ca\u5f97\u5230<\/span>Abemaciclib (Bemaciclib)\u3002<\/span><\/span><\/h1>\n


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

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


<\/p>\n

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CDK4\/6\u6291\u5236\u5242\u540c\u9776\u70b9\u7684\u836f\u7269<\/span><\/span><\/strong><\/o:p><\/span><\/strong><\/h1>\n<\/section>\n<\/section>\n

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

2017\u5e74<\/span>8\u6708\uff0c<\/span>Nature\u4e0a\u7684\u4e00\u9879\u7814\u7a76\u79f0\uff0c<\/span>1\u5e74\u5356<\/span>20\u4ebf\u7684<\/span>\u201c\u91cd\u78c5\u6297\u764c\u836f<\/span>\u201dCDK4\/6\u6291\u5236\u5242\u7adf\u7136\u4e5f\u662f\u514d\u75ab\u7597\u6cd5\uff0cCDK4\/6\u8be5\u9776\u70b9\u5f15\u8d77\u4e86\u5927\u5bb6\u7684\u5f3a\u70c8\u5173\u6ce8\u3002<\/span>\u76ee\u524d\uff0c<\/span>CDK4\/6\u6291\u5236\u5242\u5728\u7814\u4ea7\u54c1\u5982\u4e0b\uff1a<\/span><\/strong><\/span><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff0c\u4e73\u817a\u764c\u6f5c\u529b\u9776\u70b9CDK4\/6\u8c03\u7814\u62a5\u544a\"<\/p>\n


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\u7ed3\u8bed<\/span><\/strong><\/o:p><\/span><\/strong><\/p>\n<\/section>\n<\/section>\n


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CDK4\/6\u6291\u5236\u5242\u88ab\u7eb3\u5165<\/span>ER+\/HER2- <\/span>\u665a\u671f\u4e73\u817a\u764c\u7684\u6cbb\u7597\u65b9\u6848\uff0c\u771f\u7684\u6539\u53d8\u4e86\u75be\u75c5\u7684\u81ea\u7136\u75c5\u7a0b\uff0c\u8d8a\u6765\u8d8a\u591a\u7684<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\u66f4\u5e7f\u6cdb\u5730\u5e94\u7528\u4e8e\u4e34\u5e8a\uff0c\u8fd9\u7c7b\u836f\u7269\u5728\u5176\u4ed6\u80bf\u7624\u5305\u62ec\u8102\u80aa\u8089\u7624\u3001\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u3001\u5957\u7ec6\u80de\u6dcb\u5df4\u7624\uff0c\u9ed1\u7d20\u7624\u548c\u6210\u80f6\u8d28\u7ec6\u80de\u7624\u4e5f\u663e\u793a\u6297\u80bf\u7624\u6d3b\u6027\u3002\u300a<\/span>Nature<\/span>\u300b\u6700\u65b0\u7814\u7a76\u663e\u793a\uff0c<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\u4e0d\u5355\u662f\u963b\u65ad\u4e86\u5b9e\u4f53\u7624\u7684\u7ec6\u80de\u5468\u671f\uff0c\u540c\u65f6\u5728\u514d\u75ab\u589e\u5f3a\u65b9\u9762\u6709\u4e00\u4e9b\u6548\u5e94\u3002\u5bf9\u4e8e\u4e09\u9634\u6027\u4e73\u817a\u764c\u91c7\u7528\u514d\u75ab\u6cbb\u7597\u8054\u5408<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\uff0c\u5176\u7ed3\u679c\u62ed\u76ee\u4ee5\u5f85\u3002<\/span>CDK4\/6<\/span>\u6291\u5236\u5242\u662f\u5f88\u6709\u524d\u666f\u7684\u836f\u7269\uff0c\u672a\u6765\u6709\u66f4\u591a\u5229\u7528\u7a7a\u95f4\u3002<\/span><\/span><\/p>\n

 <\/span><\/strong><\/span><\/p>\n

\u53c2\u8003\u6587\u732e<\/span><\/strong>\uff1a<\/span><\/strong><\/span><\/p>\n

[1]. Huober J and Thurlimann B. Breast Care 2009; 4:367-372.<\/span><\/p>\n

[2]CA CANCER J CLIN 2018;0:1\u201331<\/span><\/p>\n

[3] \u5218\u7956\u5b8f<\/span>, <\/span>\u502a\u4ef0\u9e4f<\/span>, <\/span>\u9ec4\u7eee\u56fd<\/span>, <\/span>\u8bb8\u6587\u5175<\/span>, <\/span>\u9648\u5b8b\u94a6<\/span>. <\/span>\u4e73\u817a\u764c\u65b0\u5206\u5b50\u5206\u578b\u4e2d\u7684<\/span>P53<\/span>\u86cb\u767d\u8868\u8fbe\u53ca\u4e34\u5e8a\u8bc4\u4f30<\/span>[J].<\/span> \u65b0\u533b\u5b66<\/span>, 2013, 44(3): 166-168.<\/span><\/p>\n

[4] Finn R S, Crown J P, Lang I, et al. The cyclin-dependent kinase 4\/6 inhibitor palbociclib in combination with letrozole versus letrozole aloneas first-line treatment of oestrogen receptor-positive, HER2-negative,advanced breast cancer (PALOMA-1\/TRIO-18): a randomised phase 2study[J]. Lancet Oncol, 2015, 16(1): 25-35.<\/span><\/p>\n

[5] Turner N C, Ro J, Andr\u00e9 F, et al. Palbociclib in hormone-receptor-positive advanced breast cancer[J]. N Engl J Med, 2015, 373(3): 209-219.<\/span><\/p>\n

[6] Erdman  D  T,  Flamme  C  M,  Nelson  J  D.  Preparation  of2-(pyridin<\/span><\/p>\n

-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones  [P]. WO: 2008032157, 2007-08-27.<\/span><\/p>\n

[7]\u79d1\u777f\u552f\u5b89\uff1a<\/span>2017<\/span>\u5e74\u6700\u503c\u5f97\u5173\u6ce8\u7684\u836f\u7269\u9884\u6d4b\uff08\u5168\u6587\u62a5\u544a\uff09<\/span>.[2017\/04\/14]. <\/span>http:\/\/ip-science.thomsonreuters.com.cn\/lscn\/ls-blog\/20170414_2.shtml<\/span><\/p>\n

[8] Gilbert B, Christopfer T B, Clinton A B, et al. Pyrrolopyrimidinecompounds as CDK inhibitors [P]. WO: 2010\/020675 A1,2009-08-20.<\/span><\/p>\n

[9] Calienni J V, Chen G, Gong B, et al. Salt(s)of7-cyclopentyl-2-(5-piperazin-1-yl-p<\/span><\/p>\n

yridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide<\/span><\/p>\n

and processes of making thereof [P]. US: 2012\/0115878A1, 2012-05-10.<\/span><\/p>\n

[10] Dickler M N, Tolaney S M, Rugo H S, et al. MONARCH 1, a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent,in patients with refractory[J]. Clin Cancer Res, 2017, 23(17):5218-5224.<\/span><\/p>\n

[11] Sledge G W Jr, Toi M, Neven P, et al. MONARCH 2: Abemaciclib incombination with fulvestrant in women with HR+\/HER-2 advancedbreast cancer who had progressed while receiving endocrinetherapy[J]. J Clin Oncol, 2017, 35(25):2875-2884.<\/span><\/p>\n

[12] Goetz M P, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer[J]. J Clin Oncol, 2017,35(32):3638-3646.<\/span><\/p>\n

 [13] US20100160340<\/span><\/p>\n


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\u6392\u7248\uff1a\u9621\u4e0a\u964c\u964c<\/span><\/p>\n


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\u57f9\u8bad\u548c\u4f1a\u8bae\uff1a<\/p>\n