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\u3000\u3000\u505aKRAS G12C\u76f8\u5173\u975e\u4e34\u5e8a\u7814\u7a76\uff0c\u4e0d\u5c11\u79d1\u7814\u4eba\u90fd\u5728\u627e\u5b9e\u9a8c\u5ba4\u7528\u7684\u591a\u7684Adagrasib\u5382\u5546\uff0c\u9760\u8c31\u7684Adagrasib\u5382\u5bb6\u66f4\u662f\u79d1\u7814\u9879\u76ee\u987a\u5229\u63a8\u8fdb\u7684\u5173\u952e\u4fdd\u969c\u3002<\/p>\n

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<\/p>\n

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\u3000\u3000\u56e0\u6b64\uff0c\u5f88\u591a\u79d1\u7814\u4eba\u5458\u90fd\u5728\u641c\u7d22\u5b9e\u9a8c\u5ba4\u7528\u7684\u591a\u7684Adagrasib\u5382\u5bb6\uff0c\u60f3\u8981\u627e\u5230\u9760\u8c31\u7684Adagrasib\u5382\u5bb6\u6765\u4fdd\u969c\u5b9e\u9a8c\u6570\u636e\u7684\u53ef\u9760\u6027\u3002\u5728\u4f17\u591a\u4f9b\u5e94\u5546\u4e2d\uff0cTargetMol\u51ed\u501f\u7a33\u5b9a\u7684\u4ea7\u54c1\u54c1\u8d28\u548c\u5b8c\u5584\u7684\u6280\u672f\u670d\u52a1\uff0c\u83b7\u5f97\u4e86\u5168\u7403\u79d1\u7814\u7528\u6237\u7684\u5e7f\u6cdb\u8ba4\u53ef\u3002TargetMol\u7684\u7efc\u5408\u4f18\u52bf\uff0c\u53ef\u4ee5\u4ece\u56db\u4e2a\u6838\u5fc3\u7ef4\u5ea6\u6765\u68b3\u7406\u3002<\/p>\n

\u786c\u6838\u9776\u70b9\u9a8c\u8bc1\uff0c\u673a\u5236\u6e05\u6670\u6d3b\u6027\u4f18\u5f02<\/h3>\n

\u3000\u3000Adagrasib\u4e5f\u5c31\u662f\u963f\u8fbe\u683c\u62c9\u897f\u5e03\uff0c\u4e5f\u53ebMRTX849\uff0cCAS\u53f72326521-71-3\uff0c\u4f5c\u4e3a\u4e00\u6b3e\u53e3\u670d\u6709\u6548\u3001\u9ad8\u9009\u62e9\u6027\u7684KRAS G12C\u5171\u4ef7\u6291\u5236\u5242\uff0c\u5176\u4f5c\u7528\u673a\u5236\u660e\u786e\uff0c\u6d3b\u6027\u6570\u636e\u7ecf\u8fc7\u591a\u8f6e\u9a8c\u8bc1\u3002<\/p>\n

\u3000\u3000\u5b83\u901a\u8fc7\u4e0d\u53ef\u9006\u5730\u7ed3\u5408KRAS G12C\u7a81\u53d8\u86cb\u767d\u7684\u534a\u80f1\u6c28\u917812\u6b8b\u57fa\uff0c\u5c06\u86cb\u767d\u9501\u5b9a\u5728\u975e\u6d3b\u6027\u7684GDP\u7ed3\u5408\u6784\u8c61\u4e2d\uff0c\u963b\u65adKRAS\u53ca\u5176\u4e0b\u6e38MAPK\/ERK\u548cPI3K\/AKT\u7b49\u81f4\u764c\u4fe1\u53f7\u901a\u8def\u7684\u4f20\u5bfc\u3002<\/p>\n

\u3000\u3000\u8fd9\u79cd\u7ed3\u5408\u4f9d\u8d56KRAS\u7279\u6709\u7684H95\u5f00\u5173-II\u53e3\u888b\u6b8b\u57fa\uff0c\u8be5\u6b8b\u57fa\u5728HRAS\u6216NRAS\u4e2d\u5e76\u4e0d\u5b58\u5728\uff0c\u56e0\u6b64\u5bf9KRAS G12C\u7684\u9009\u62e9\u6027\u6781\u9ad8\uff0c\u5bf9\u91ce\u751f\u578bKRAS\u6216\u975eG12C\u7a81\u53d8\u7ec6\u80de\u5f71\u54cd\u6781\u5c0f\uff0c\u4ece\u6839\u6e90\u4e0a\u964d\u4f4e\u4e86\u5b9e\u9a8c\u7ed3\u679c\u8bef\u5224\u7684\u53ef\u80fd\u6027\u3002<\/p>\n

\u3000\u3000\u5728\u4f53\u5916\u7ec6\u80de\u6d3b\u6027\u9a8c\u8bc1\u4e2d\uff0c\u672c\u54c1\u572817\u4e2aKRAS G12C\u7a81\u53d8\u7ec6\u80de\u7cfb\u4e2d\u6709\u6548\u6291\u5236\u7ec6\u80de\u751f\u957f\uff0cIC50\u503c\u8303\u56f4\u572810-973 nM;\u5728NCI-H358\u80ba\u764c\u7ec6\u80de\u4e2d\u6291\u5236p-ERK\u6c34\u5e73\u7684IC50\u4ec5\u4e3a14 nM\uff0c\u5bf9\u975eKRAS G12C\u7a81\u53d8\u7ec6\u80de\u7684IC50\u503c\u5219\u5927\u4e8e1 \u00b5M\uff0c\u6d3b\u6027\u5dee\u5f02\u6e05\u6670\uff0c\u5b8c\u5168\u6ee1\u8db3\u673a\u5236\u7814\u7a76\u7684\u9700\u6c42\u3002<\/p>\n

\u3000\u3000\u5728\u4f53\u5185\u6d3b\u6027\u9a8c\u8bc1\u4e2d\uff0cAdagrasib\u5728\u643a\u5e26KRAS G12C\u7a81\u53d8\u80bf\u7624\u7684\u5f02\u79cd\u79fb\u690d\u6a21\u578b\u4e2d\uff0c1-100 mg\/kg\u53e3\u670d\u7ed9\u836f\u5c31\u8868\u73b0\u51fa\u660e\u786e\u7684\u5242\u91cf\u4f9d\u8d56\u6027\u6297\u80bf\u7624\u7597\u6548\uff0c\u4e3a\u4f53\u5185\u5b66\u7814\u7a76\u63d0\u4f9b\u4e86\u53ef\u9760\u7684\u6d3b\u6027\u53c2\u8003\u3002<\/p>\n

\u3000\u3000\u4e34\u5e8a\u7814\u7a76\u6570\u636e\u4e5f\u8fdb\u4e00\u6b65\u9a8c\u8bc1\u4e86\u5176\u6d3b\u6027\u4ef7\u503c\uff1aAdagrasib\u5355\u836f\u6cbb\u7597KRAS G12C\u7a81\u53d8\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u7684\u5ba2\u89c2\u7f13\u89e3\u7387\u8fbe41.4%;\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\uff0cAdagrasib\u8054\u5408\u897f\u59a5\u6614\u5355\u6297\u7684\u5ba2\u89c2\u7f13\u89e3\u7387\u4e3a34%\uff0c\u4e2d\u4f4d\u603b\u751f\u5b58\u671f\u8fbe15.9\u4e2a\u6708\uff0c\u8be5\u8054\u5408\u65b9\u6848\u5df2\u4e8e2024\u5e74\u83b7\u5f97FDA\u52a0\u901f\u6279\u51c6\uff0c\u6d3b\u6027\u8f6c\u5316\u6027\u5f97\u5230\u4e34\u5e8a\u786e\u8ba4\u3002<\/p>\n

\u4e25\u82db\u8d28\u63a7\u6807\u51c6\uff0c\u4ea7\u54c1\u54c1\u8d28<\/h3>\n

\u3000\u3000\u5bf9\u4e8e\u79d1\u7814\u7528\u5c0f\u5206\u5b50\u6291\u5236\u5242\u6765\u8bf4\uff0c\u7eaf\u5ea6\u76f4\u63a5\u51b3\u5b9a\u4e86\u5b9e\u9a8c\u6570\u636e\u7684\u53ef\u9760\u6027\uff0cTargetMol\u5bf9\u672c\u54c1\u6267\u884c\u5168\u94fe\u8def\u6807\u51c6\u5316\u8d28\u63a7\uff0c\u4ea7\u54c1\u54c1\u8d28\u8fbe\u5230\u6c34\u5e73\u3002<\/p>\n

\u3000\u3000TargetMol\u662f\u5168\u7403\u5c0f\u5206\u5b50\u5316\u5408\u7269\u3001\u6291\u5236\u5242\u4e0e\u751f\u7269\u8bd5\u5242\u77e5\u540d\u79d1\u7814\u54c1\u724c\uff0c\u6301\u6709ISO9001\u8d28\u91cf\u7ba1\u7406\u4f53\u7cfb\u8ba4\u8bc1\u4e0eISO17025\u5b9e\u9a8c\u5ba4\u68c0\u6d4b\u8d44\u8d28\u8ba4\u8bc1\uff0c\u4ece\u539f\u6599\u5165\u5e93\u3001\u5408\u6210\u5236\u5907\u3001\u68c0\u6d4b\u5206\u88c5\u5230\u4ed3\u50a8\u7269\u6d41\u5168\u6d41\u7a0b\u90fd\u6267\u884c\u6807\u51c6\u5316\u7ba1\u63a7\uff0c\u6bcf\u4e00\u6279\u6b21\u4ea7\u54c1\u90fd\u53ef\u4ee5\u63d0\u4f9b\u5b8c\u6574\u68c0\u6d4b\u6570\u636e\uff0c\u4fdd\u969c\u5b9e\u9a8c\u6570\u636e\u53ef\u91cd\u590d\u3001\u7ed3\u679c\u7a33\u5b9a\u53ef\u9760\u3002<\/p>\n

\u3000\u3000\u672c\u54c1\u7eaf\u5ea6\u7ecfHPLC\u9a8c\u8bc1\u9ad8\u8fbe99.9%\uff0c\u6781\u9ad8\u7eaf\u5ea6\u4ece\u6839\u6e90\u4e0a\u6392\u9664\u4e86\u6742\u8d28\u5bf9\u5b9e\u9a8c\u7ed3\u679c\u7684\u5e72\u6270\uff0c\u8ba9\u7814\u7a76\u8005\u53ef\u4ee5\u51c6\u786e\u5c06\u89c2\u5bdf\u5230\u7684\u4fe1\u53f7\u901a\u8def\u6291\u5236\u548c\u6297\u589e\u6b96\u6548\u5e94\uff0c\u660e\u786e\u5f52\u56e0\u4e8eKRAS G12C\u7684\u5171\u4ef7\u5360\u636e\uff0c\u907f\u514d\u4e86\u6742\u8d28\u5e26\u6765\u7684\u5047\u9633\u6027\u7ed3\u679c\uff0c\u63d0\u5347\u4e86\u5b9e\u9a8c\u7ed3\u8bba\u7684\u53ef\u4fe1\u5ea6\u3002<\/p>\n

\u3000\u3000\u4ea7\u54c1\u8fd8\u5177\u5907\u4f18\u5f02\u7684\u6eb6\u89e3\u6027\u548c\u7a33\u5b9a\u6027\uff0c\u5728DMSO\u4e2d\u6eb6\u89e3\u5ea6\u53ef\u8fbe242 mg\/mL\uff0c\u5b8c\u5168\u6ee1\u8db3\u7ec6\u80de\u5b9e\u9a8c\u548c\u9ad8\u5242\u91cf\u4f53\u5185\u5b9e\u9a8c\u7684\u914d\u5236\u9700\u6c42\uff0c\u540c\u65f6\u8fd8\u4e3a\u79d1\u7814\u4eba\u5458\u63d0\u4f9b\u4e8610% DMSO+40% PEG300+5% Tween 80+45% Saline\u7684\u4f53\u5185\u5b9e\u9a8c\u914d\u65b9\u53c2\u8003\uff0c\u53ef\u76f4\u63a5\u914d\u523610 mg\/mL\u6df7\u60ac\u6db2\uff0c\u7b80\u5316\u4e86\u5b9e\u9a8c\u64cd\u4f5c\u6d41\u7a0b\u3002<\/p>\n

\u3000\u3000\u50a8\u5b58\u7a33\u5b9a\u6027\u4e5f\u80fd\u6ee1\u8db3\u79d1\u7814\u5b9e\u9a8c\u5ba4\u7684\u957f\u671f\u4f7f\u7528\u9700\u6c42\uff0c\u7c89\u672b\u53ef\u5728-20\u00b0C\u6761\u4ef6\u4e0b\u7a33\u5b9a\u4fdd\u5b583\u5e74\uff0c\u6eb6\u4e8e\u6eb6\u5242\u540e\u7f6e\u4e8e-80\u00b0C\u53ef\u4fdd\u5b581\u5e74\uff0c\u6279\u6b21\u95f4\u7a33\u5b9a\u6027\u4f18\u5f02\uff0c\u4e0d\u4f1a\u56e0\u4e3a\u50a8\u5b58\u65f6\u95f4\u53d8\u5316\u5f71\u54cd\u5b9e\u9a8c\u7ed3\u679c\uff0c\u957f\u671f\u4f7f\u7528\u7684\u4e00\u81f4\u6027\u66f4\u597d\u3002<\/p>\n

\u5b8c\u5584\u6570\u636e\u652f\u6491\uff0c\u89e3\u51b3\u79d1\u7814\u5168\u6d41\u7a0b\u75db\u70b9<\/h3>\n

\u3000\u3000\u4e0d\u540c\u4e8e\u5f88\u591a\u4ec5\u63d0\u4f9b\u5316\u5408\u7269\u7684\u4f9b\u5e94\u5546\uff0cTargetMol\u7684\u8fd9\u6b3eAdagrasib\u63d0\u4f9b\u4e86\u5b8c\u6574\u7684\u5b9e\u9a8c\u76f8\u5173\u6570\u636e\uff0c\u80fd\u591f\u89e3\u51b3\u79d1\u7814\u4eba\u5458\u4ece\u5b9e\u9a8c\u8bbe\u8ba1\u5230\u7ed3\u679c\u5206\u6790\u5168\u6d41\u7a0b\u7684\u591a\u4e2a\u6838\u5fc3\u75db\u70b9\u3002<\/p>\n

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\u3000\u3000\u540c\u65f6\u660e\u786e\u4e86Adagrasib\u662fCYP3A4\u7684\u5f3a\u6291\u5236\u5242\uff0c\u7a33\u6001\u4e0b\u53ef\u4f7f\u53e3\u670d\u66b4\u9732\u589e\u52a021\u500d\uff0c\u8fd9\u4e00\u7279\u6027\u5bf9\u4e8e\u7814\u7a76\u8005\u8bbe\u8ba1\u8054\u5408\u7528\u836f\u5b9e\u9a8c\uff0c\u6bd4\u5982\u76ee\u524d\u70ed\u95e8\u7684Adagrasib\u4e0e\u897f\u59a5\u6614\u5355\u6297\u8054\u7528\u65b9\u6848\uff0c\u81f3\u5173\u91cd\u8981\uff0c\u53ef\u4ee5\u5e2e\u52a9\u7814\u7a76\u8005\u63d0\u524d\u89c4\u907f\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u5e26\u6765\u7684\u5b9e\u9a8c\u8bbe\u8ba1\u504f\u5dee\u3002<\/p>\n

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