{"id":1315,"date":"2024-02-18T15:42:51","date_gmt":"2024-02-18T07:42:51","guid":{"rendered":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1315"},"modified":"2024-02-19T10:50:18","modified_gmt":"2024-02-19T02:50:18","slug":"acs-pharmacology-translational-science-%e4%b8%80%e7%9f%b3%e4%b8%89%e9%b8%9f%ef%bc%9a%e9%bb%84%e7%89%9b%e5%ae%9e%e9%aa%8c%e5%ae%a4%e5%88%a9%e7%94%a8%e5%8f%8d%e5%90%91%e5%85%b1%e4%bb%b7%e5%af%b9","status":"publish","type":"post","link":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1315","title":{"rendered":"ACS Pharmacology & Translational Science | \u4e00\u77f3\u4e09\u9e1f\uff1a\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u5229\u7528\u53cd\u5411\u5171\u4ef7\u5bf9\u63a5\u7b5b\u9009\u65b9\u6cd5\u53d1\u73b0\u8001\u836fEntacapone\u7684\u65b0\u9776\u6807KEAP1"},"content":{"rendered":"\n

1988\u5e74\u8bfa\u8d1d\u5c14\u751f\u7406\u5b66\u548c\u533b\u5b66\u5956\u83b7\u5f97\u8005Sir James Black \u6709\u4e00\u53e5\u540d\u8a00: ‘The most fruitful basis of the discovery of a new drug is to start with an old drug’\u3002\u53d1\u73b0\u4e00\u4e2a\u8001\u836f\u7684\u65b0\u9776\u70b9\u6216\u4f5c\u7528\u673a\u5236\uff0c\u5bf9\u4e8e\u836f\u7406\u5b66\u5bb6\u800c\u8a00\uff0c\u5c31\u50cf\u751f\u7269\u5b66\u5bb6\u53d1\u73b0\u4e00\u4e2a\u57fa\u56e0\u6216\u86cb\u767d\u7684\u65b0\u529f\u80fd\u4e00\u6837\u91cd\u8981\u3002<\/p>\n\n\n\n

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Entacapone (ENT)<\/figcaption><\/figure><\/div>\n\n\n\n

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\"\"<\/a>
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\u57fa\u4e8e\u4ee5\u4e0a\u5b9e\u9a8c\u7ed3\u679c\uff0c\u6211\u4eec\u8fdb\u4e00\u6b65\u68c0\u6d4b\u4e86Entacapone\u548cNitecapone\u5728\u5c0f\u9f20\u4f53\u5185\u7684\u6d3b\u6027\uff08\u56fe5\uff09\u3002\u5728\u5206\u79bb\u8bf1\u5bfc\u7684BMDMs\u7ec6\u80de\u4e2d\uff0c\u6211\u4eec\u53d1\u73b0Entacapone\u6216\u8005Nitecapone\u5904\u7406\u540e\uff0c\u80fd\u6fc0\u6d3b\u53d7NRF2\u8c03\u8282\u7684\u4e0b\u6e38AREs\u5143\u4ef6\uff0c\u5e76\u4e14\u5728COMT\u6216\u8005FTO KO\u7684\u7ec6\u80de\u4e2d\u4ecd\u7136\u80fd\u591f\u6fc0\u6d3bNRF2\u4e0b\u6e38\uff0c\u8bf4\u660eEntacapone\u548cNitecapone\u5728\u8fd9\u6761\u901a\u8def\u4e0a\u4e0d\u4f9d\u8d56\u4e8eCOMT\u6216FTO\u53d1\u6325\u4f5c\u7528\u3002\u66f4\u8fdb\u4e00\u6b65\uff0c\u6211\u4eec\u7528Entacapone\u6216\u8005Nitecapone\u5904\u7406\u5c0f\u9f20\uff0c\u5728\u8840\u6db2\u4e2d\u4e5f\u68c0\u6d4b\u5230\u4e86\u53d7NRF2\u8c03\u8282\u7684\u4e0b\u6e38GDF15\u7684\u86cb\u767d\u6c34\u5e73\u7684\u4e0a\u5347\u3002\u5e76\u4e14\uff0c\u5728MSU\u8bf1\u5bfc\u7684\u98ce\u6e7f\u6027\u5173\u8282\u708e\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u7ecfEntacapone\u6216\u8005Nitecapone\u5904\u7406\u540e\u53ef\u4ee5\u660e\u663e\u7f13\u89e3\u708e\u75c7\u75c7\u72b6\uff1b\u6b64\u5916\uff0c\u6211\u4eec\u53d1\u73b0\u836f\u7269Entacapone\u5bf9\u809d\u4e2dNRF2\u4e0b\u6e38\u6fc0\u6d3b\u66f4\u660e\u663e\uff0c\u800cNitecapone\u5bf9\u80be\u4e2dNRF2\u4e0b\u6e38\u6fc0\u6d3b\u66f4\u660e\u663e\u3002\u836f\u7269\u5728\u7ec4\u7ec7\u4e2d\u5206\u5e03\u7684\u6570\u636e\u663e\u793a\uff0c\u8fd9\u79cd\u4e0d\u540c\u7ec4\u7ec7\u7684\u6fc0\u6d3b\u8d8b\u52bf\u540c\u836f\u7269\u7684\u7ec4\u7ec7\u5206\u5e03\u543b\u5408\u3002<\/p>\n\n\n\n

\"\"<\/a>
\u56fe5\uff1a\uff08A\uff09ENT\u548cNIT\u53ef\u4ee5\u6fc0\u6d3b\u8840\u6db2\u4e2dGDF15\u7684\u8868\u8fbe\u3002\uff08B-C\uff09ENT\u548cNIT\u7f13\u89e3MSU\u8bf1\u5bfc\u7684\u5c0f\u9f20\u6025\u6027\u75db\u98ce\u6a21\u578b\u3002<\/figcaption><\/figure><\/div>\n\n\n\n

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

\u7efc\u4e0a\uff0c\u6211\u4eec\u7684\u7814\u7a76\u4eae\u70b9\uff1a<\/p>\n\n\n\n

  1. \u57fa\u4e8e\u53cd\u5411\u5171\u4ef7\u5bf9\u63a5\uff0c\u6211\u4eec\u53d1\u73b0Entacapone\u8fd9\u7c7b\u542b\u6709\u4eb2\u7535\u57fa\u56e2\u7684COMT\u6291\u5236\u5242\uff0c\u4ee5\u53ef\u9006\u5171\u4ef7\u7684\u65b9\u5f0f\u7ed3\u5408KEAP1\uff0c\u5c55\u793a\u4e86\u4e00\u79cd\u836f\u7269\u4ee5\u4e0d\u540c\u7ed3\u5408\u65b9\u5f0f\u7ed3\u5408\u4e0d\u540c\u9776\u6807\u7684\u73b0\u8c61\u3002<\/li>
  2. \u6211\u4eec\u53d1\u73b0\u4e86Nitecapone\u4e2d3-\u4e9a\u7532\u57fa-\u4e59\u9170\u4e19\u916e\u7ed3\u6784\u5355\u5143\u662f\u4e00\u79cd\u65b0\u578b\u7684\u53ef\u9006\u5171\u4ef7\u5f39\u5934\uff0c\u5177\u6709\u8fdb\u4e00\u6b65\u5f00\u53d1\u5e94\u7528\u7684\u6f5c\u529b\u3002<\/li>
  3. Entacapone\u548cNitecapone\u5728\u4f53\u5916\u3001\u4f53\u5185\u5b9e\u9a8c\u4e2d\uff0c\u5747\u8868\u73b0\u51fa\u5bf9KEAP1\/NRF2\u901a\u8def\u4e2d\u6297\u6c27\u5316\u5e94\u6fc0\u5143\u4ef6\u57fa\u56e0\u8868\u8fbe\u7684\u6fc0\u6d3b\u3002<\/li>
  4. \u8fd9\u4e24\u79cd\u836f\u7269\u5206\u5b50\u5728\u5c0f\u9f20\u6025\u6027\u75db\u98ce\u6a21\u578b\u4e2d\u8868\u73b0\u51fa\u6297\u708e\u6d3b\u6027\uff0c\u8868\u660e\u5b83\u4eec\u662f\u4e00\u7c7b\u65b0\u578b\u7684\u53e3\u670d\u6709\u6548\u7684KEAP1\u53ef\u9006\u5171\u4ef7\u7ed3\u5408\u5206\u5b50\u3002<\/li>
  5. \u63d0\u4f9b\u4e86\u5728\u7ed3\u6784\u86cb\u767d\u7ec4\u5b66\u6c34\u5e73\u7814\u7a76\u53ef\u9006\u5171\u4ef7\u7684\u8303\u5f0f\u793a\u4f8b\u3002<\/li><\/ol>\n\n\n\n

    Entacapone\u81ea\u6700\u521d\u9776\u5411COMT\u4e00\u4e3e\u6210\u540d\uff0c\u540e\u6765\u53c8\u53d1\u73b0\u5b83\u540c\u65f6\u662fFTO\u6291\u5236\u5242\uff0c\u73b0\u5728\u53c8\u88ab\u53d1\u73b0\u53ef\u4ee5\u4f5c\u4e3aKEAP1\u8c03\u8282\u5242\u3002\u6211\u4eec\u5bf9\u4e8e\u4e8b\u7269\u7684\u8ba4\u77e5\uff0c\u603b\u662f\u968f\u7740\u79d1\u5b66\u7684\u4e0d\u65ad\u63a2\u7d22\u800c\u62d3\u5c55\u548c\u6df1\u5165\uff0c\u4e0e\u6b64\u540c\u65f6\uff0c\u8ba1\u7b97\u65b9\u6cd5\u548c\u5de5\u5177\u4e5f\u8d4b\u4e88\u4e86\u6211\u4eec\u66f4\u7406\u6027\u548c\u66f4\u7ecf\u6d4e\u7684\u4f18\u52bf\u3002\u65b0\u836f\u7814\u53d1\u7eb7\u7e41\u590d\u6742\u5374\u53c8\u5145\u6ee1\u9b45\u529b\uff0c\u5176\u4e2d\u5c0f\u5206\u5b50\u836f\u7269\u7684\u591a\u9776\u6807\u4f5c\u7528\u662f\u7279\u8272\u6240\u5728\uff0c\u5b83\u4eec\u662f”\u4e00\u4e13\u591a\u80fd”\uff0c\u8fd8\u662f”\u529f\u8fc7\u53c2\u534a”\uff0c\u53d6\u51b3\u4e8e\u4e25\u8c28\u7684\u9776\u70b9\u548c\u4f5c\u7528\u673a\u5236\u7684\u79d1\u5b66\u7814\u7a76\u3002\u62d3\u5c55\u5c0f\u5206\u5b50\u5316\u5408\u7269\u7684\u65b0\u5316\u5b66\u7a7a\u95f4\u662f\u76ee\u524d\u70ed\u70b9\uff0c\u4f46\u4ece\u5df2\u6709\u836f\u7269\u7684\u5316\u5b66\u7a7a\u95f4\u62d3\u5c55\u65b0\u9776\u70b9\u4e5f\u662f\u5fc5\u4e0d\u53ef\u5c11\u7684\uff0c\u4e24\u8005\u76f8\u8f85\u76f8\u6210\uff0c\u76f8\u5f97\u76ca\u5f70\u3002Entacapone\u7684\u4e00\u77f3\u4e09\u9e1f\uff0c\u53ef\u80fd\u53ea\u662f\u8fd9\u4e2a\u6545\u4e8b\u7684\u5f00\u59cb\u3002<\/p>\n\n\n\n

    \u9ec4\u725b\u5b9e\u9a8c\u5ba4\u7684\u535a\u58eb\u7814\u7a76\u751f\u738b\u5e73\u4e0e\u674e\u6768\u535a\u58eb\u4e3a\u672c\u6587\u5171\u540c\u7b2c\u4e00\u4f5c\u8005\uff0c\u9ec4\u725b\u535a\u58eb\u4e3a\u901a\u8baf\u4f5c\u8005\u3002\u5176\u4ed6\u4f5c\u8005\u5305\u62ec\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u7684\u6768\u4ec5\u4ea6\uff0c\u674e\u5b50\u95ee\u535a\u58eb\uff0c\u4efb\u6b23\u6850\uff0c\u674e\u9e4f\u98de\uff0c\u79e6\u9e7f\u67d8\uff0c\u8c22\u94b0\u5a77\uff0c\u4faf\u6960\u6960\uff1b\u4ee5\u53ca\u4e2d\u56fd\u519c\u4e1a\u79d1\u5b66\u9662\u5b5f\u5e86\u77f3\u535a\u58eb\uff1b\u745e\u749e\u946b\uff08\u82cf\u5dde\uff09\u751f\u7269\u79d1\u6280\u6709\u9650\u516c\u53f8\u7684\u674e\u4f1f\u535a\u58eb\uff1b\u8be5\u7814\u7a76\u5de5\u4f5c\u8fd8\u5f97\u5230\u4e86NIBS\u86cb\u767d\u8d28\u4e2d\u5fc3\u548c\u4ee3\u8c22\u7ec4\u5b66\u4e2d\u5fc3\u7684\u652f\u6301\u3002\u8be5\u7814\u7a76\u7531\u5317\u4eac\u5e02\u79d1\u59d4\uff08Z201100005320012\uff09\u548c\u6e05\u534e\u5927\u5b66\u5171\u540c\u8d44\u52a9\u3002<\/p>\n\n\n\n

    \u8bba\u6587\u94fe\u63a5<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

    1988\u5e74\u8bfa\u8d1d\u5c14\u751f\u7406\u5b66\u548c\u533b\u5b66\u5956\u83b7\u5f97\u8005Sir James Black \u6709\u4e00\u53e5\u540d\u8a00: ‘The most fruitful basis of the discovery of a new drug is to start with an old drug’\u3002\u53d1\u73b0\u4e00\u4e2a\u8001\u836f\u7684\u65b0\u9776\u70b9\u6216\u4f5c\u7528\u673a\u5236\uff0c\u5bf9\u4e8e\u836f\u7406\u5b66\u5bb6\u800c\u8a00\uff0c\u5c31\u50cf\u751f\u7269\u5b66\u5bb6\u53d1\u73b0\u4e00\u4e2a\u57fa\u56e0\u6216\u86cb\u767d\u7684\u65b0\u529f\u80fd\u4e00\u6837\u91cd\u8981\u3002 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