{"id":12218,"date":"2020-12-02T07:03:00","date_gmt":"2020-12-02T00:03:00","guid":{"rendered":"https:\/\/www.xinwengao.com\/cn\/pr\/2020120207030012218"},"modified":"2020-12-02T09:15:05","modified_gmt":"2020-12-02T01:15:05","slug":"%e4%ba%9a%e7%9b%9b%e5%8c%bb%e8%8d%afmdm2-p53%e6%8a%91%e5%88%b6%e5%89%82apg-115%e5%8d%95%e8%8d%af%e6%88%96%e8%81%94%e5%90%88bcl-2%e6%8a%91%e5%88%b6%e5%89%82apg-2575%e6%b2%bb%e7%96%97%e5%a4%8d%e5%8f%91","status":"publish","type":"post","link":"https:\/\/www.xinwengao.com\/cn\/pr\/2020120207030012218","title":{"rendered":"\u4e9a\u76db\u533b\u836fMDM2-p53\u6291\u5236\u5242APG-115\u5355\u836f\u6216\u8054\u5408Bcl-2\u6291\u5236\u5242APG-2575\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbbT-\u5e7c\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\u7684IIa\u671f\u4e34\u5e8a\u7814\u7a76\u83b7\u4e2d\u7f8e\u4e24\u56fd\u4e34\u5e8a\u8bd5\u9a8c\u8bb8\u53ef"},"content":{"rendered":"\n\n\n
\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u4e2d\u56fd\u82cf\u5dde\u548c\u7f8e\u56fd\u9a6c\u91cc\u5170\u5dde\u7f57\u514b\u7ef4\u5c14\u5e022020\u5e7412\u67082\u65e5 \/\u7f8e\u901a\u793e\/ — \u81f4\u529b\u4e8e\u5728\u80bf\u7624\u3001\u4e59\u809d\u53ca\u4e0e\u8870\u8001\u76f8\u5173\u75be\u75c5\u7b49\u6cbb\u7597\u9886\u57df\u5f00\u53d1\u521b\u65b0\u836f\u7269\u7684\u5904\u4e8e\u4e34\u5e8a\u9636\u6bb5\u7684\u7814\u53d1\u4f01\u4e1a– \u4e9a\u76db\u533b\u836f\uff086855.HK\uff09\u4eca\u65e5\u5ba3\u5e03\uff0c\u516c\u53f8\u5728\u78141\u7c7b\u65b0\u836fMDM2-p53\u6291\u5236\u5242APG-115\u4f5c\u4e3a\u5355\u836f\u53ca\u8054\u5408\u516c\u53f8\u53e6\u4e001\u7c7b\u65b0\u836fBcl-2\u6291\u5236\u5242APG-2575\u83b7\u5f97\u56fd\u5bb6\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\u836f\u7269\u5ba1\u8bc4\u4e2d\u5fc3\uff08CDE\uff09\u7684\u4e34\u5e8a\u8bd5\u9a8c\u8bb8\u53ef\uff0c\u5c06\u5f00\u5c55\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbbT-\u5e7c\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\uff08R\/R T-PLL\uff09\u7684IIa\u671f\u4e34\u5e8a\u7814\u7a76\u3002\u6b64\u524d\u8be5\u7814\u7a76\u65b9\u6848\u5df2\u83b7\u7f8e\u56fdFDA\u4e34\u5e8a\u8bb8\u53ef\u3002<\/p>\n

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

\u8be5\u7814\u7a76\u662f\u4e00\u9879\u5168\u7403\u591a\u4e2d\u5fc3\u3001\u5f00\u653e\u3001IIa\u671f\u4e34\u5e8a\u7814\u7a76\uff0c\u65e8\u5728\u8bc4\u4ef7APG-115\u5355\u836f\u6216\u8054\u5408APG-2575\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbbT-PLL\u60a3\u8005\u7684\u5b89\u5168\u6027\u3001\u836f\u4ee3\u52a8\u529b\u5b66\u53ca\u521d\u6b65\u7597\u6548\u3002<\/p>\n

T-PLL\u4e3a\u4fb5\u88ad\u6027T\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5[1]<\/span><\/sup>\u3002\u8be5\u75be\u75c5\u975e\u5e38\u7f55\u89c1\uff0c\u4eba\u7fa4\u603b\u53d1\u75c5\u7387\u4ec50.6\/\u767e\u4e07\u4eba\uff0c\u4e2d\u4f4d\u8bca\u65ad\u5e74\u9f8461\u5c81[<\/span>2],[3]<\/span><\/sup>\u3002T-PLL\u6cbb\u7597\u9009\u62e9\u975e\u5e38\u6709\u9650\uff0c\u4e14\u5bf9\u5e38\u89c4\u5316\u7597\u4e0d\u654f\u611f\uff0c\u4e34\u5e8a\u8bd5\u9a8c\u5f88\u5c11[4<\/span>]<\/sup>\u3002\u5230\u76ee\u524d\u4e3a\u6b62\uff0c\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff08FDA\uff09\u3001\u6b27\u6d32\u836f\u54c1\u7ba1\u7406\u5c40\uff08EMA\uff09\u548c\u56fd\u5bb6\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff08NMPA\uff09\u5c1a\u672a\u6279\u51c6\u4efb\u4f55\u836f\u7269\u7528\u4e8eT-PLL\u6cbb\u7597\u3002\u590d\u53d1T-PLL\u60a3\u8005\u9884\u540e\u5f88\u5dee\uff0c\u603b\u751f\u5b58\u671f\u4ec5\u4e3a6\u81f39\u4e2a\u6708[5-8<\/span>]<\/sup>\u3002\u76ee\u524d\u5bf9\u4e8eT-PLL\u7684\u6709\u6548\u6cbb\u7597\u5c1a\u5b58\u5728\u8f83\u5927\u7684\u3001\u5c1a\u672a\u6ee1\u8db3\u7684\u4e34\u5e8a\u9700\u6c42\u3002<\/p>\n

\u9ad8\u8fbe80%-90%\u7684T-PLL\u60a3\u8005\u5b58\u5728\u5171\u6d4e\u5931\u8c03\u6bdb\u7ec6\u8840\u7ba1\u6269\u5f20\u7a81\u53d8\uff08ATM\uff09\u4f4d\u70b911q23\u7f3a\u5931\u6216\u9519\u4e49\u7a81\u53d8[9<\/span>]<\/sup>\u3002\u4e9a\u76db\u533b\u836f\u4e34\u5e8a\u524d\u7814\u7a76\u53d1\u73b0\uff0c\u5728\u591a\u4e2a\u643a\u5e26ATM\u7a81\u53d8\u7684\u60a3\u8005\u6765\u6e90\u7684\u5c0f\u9f20\u5f02\u79cd\u79fb\u690d\u7624\u52a8\u7269\u6a21\u578b\uff08PDX\uff09\u4e2d\uff0cAPG-115\u5c55\u73b0\u9ad8\u5ea6\u6297\u80bf\u7624\u6d3b\u6027\uff1b\u5728\u591a\u4e2a\u4eba\u7c7b\u8840\u6db2\u6076\u6027\u80bf\u7624\u6216\u5b9e\u4f53\u7624\u7ec6\u80de\u7cfb\uff08CDX\uff09\u53caPDX\u6a21\u578b\u4e2d\uff0cAPG-115\u548cAPG-2575\u8054\u7528\u5c55\u73b0\u9ad8\u5ea6\u534f\u540c\u4f5c\u7528\uff0c\u5e76\u663e\u8457\u589e\u5f3a\u6297\u80bf\u7624\u6d3b\u6027\u3002\u8be5\u8054\u5408\u7528\u836f\u5728\u643a\u5e26AML\uff08MV-4-11\uff09\u548cMCL\uff08Z138\uff09\u5f02\u79cd\u79fb\u690d\u7624\u52a8\u7269\u6a21\u578b\u4e2d\u8fbe\u5230100%\u7684\u7f13\u89e3\u7387\u3002<\/p>\n

APG-115\u662f\u4e9a\u76db\u533b\u836f\u81ea\u4e3b\u7814\u53d1\u7684\u53e3\u670d\u751f\u7269\u53ef\u5229\u7528\u7684\u3001\u9ad8\u9009\u62e9\u6027\u7684\u5c0f\u5206\u5b50MDM2\u6291\u5236\u5242\u3002APG-115\u5bf9MDM2\u5177\u6709\u9ad8\u5ea6\u7ed3\u5408\u4eb2\u548c\u529b\uff0c\u901a\u8fc7\u963b\u65adMDM2-p53\u76f8\u4e92\u4f5c\u7528\u4ece\u800c\u6062\u590dp53\u80bf\u7624\u6291\u5236\u6d3b\u6027\u3002APG-115\u662f\u9996\u4e2a\u5728\u4e2d\u56fd\u8fdb\u5165\u4e34\u5e8a\u9636\u6bb5\u7684MDM2-p53\u6291\u5236\u5242\uff0c\u6b63\u5728\u4e2d\u56fd\u548c\u7f8e\u56fd\u5c55\u5f00\u591a\u9879\u6cbb\u7597\u5b9e\u4f53\u7624\u53ca\u8840\u6db2\u80bf\u7624\u7684\u4e34\u5e8a\u7814\u7a76\u3002<\/p>\n

APG-2575\u662f\u4e9a\u76db\u533b\u836f\u81ea\u4e3b\u7814\u53d1\u7684\u65b0\u578b\u53e3\u670dBcl-2\u9009\u62e9\u6027\u5c0f\u5206\u5b50\u6291\u5236\u5242\uff0c\u901a\u8fc7\u9009\u62e9\u6027\u6291\u5236Bcl-2\u86cb\u767d\u6765\u6062\u590d\u80bf\u7624\u7ec6\u80de\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u673a\u5236\uff08\u7ec6\u80de\u51cb\u4ea1\uff09\uff0c\u4ece\u800c\u8fbe\u5230\u6cbb\u7597\u8840\u6db2\u53ca\u5b9e\u4f53\u80bf\u7624\u7684\u76ee\u7684\u3002APG-2575\u5bf9Bcl-2\u5177\u6709\u9ad8\u5ea6\u7684\u9009\u62e9\u6027\u3002APG-2575\u7a7f\u8fc7\u7ec6\u80de\u819c\u8fdb\u5165\u7ec6\u80de\u540e\u4e0e\u7ebf\u7c92\u4f53\u819c\u4e0a\u7684\u6297\u51cb\u4ea1\u86cb\u767dBcl-2\u7ed3\u5408\uff0c\u963b\u65adBcl-2\u4e0e\u4fc3\u51cb\u4ea1\u86cb\u767dBIM\u5f62\u6210\u86cb\u767d-\u86cb\u767d\u590d\u5408\u7269\uff0c\u91ca\u653e\u51faBIM\uff0c\u540e\u8005\u8fdb\u4e00\u6b65\u6fc0\u6d3b\u7ec6\u80de\u51cb\u4ea1\u7684\u4e00\u7cfb\u5217\u7a0b\u5e8f\uff0c\u6700\u7ec8\u5bfc\u81f4\u80bf\u7624\u7ec6\u80de\u51cb\u4ea1\u3002APG-2575\u662f\u9996\u4e2a\u5728\u4e2d\u56fd\u8fdb\u5165\u4e34\u5e8a\u9636\u6bb5\u7684\u3001\u672c\u571f\u7814\u53d1\u7684Bcl-2\u9009\u62e9\u6027\u6291\u5236\u5242\u3002\u4f5c\u4e3a\u5355\u836f\uff0cAPG-2575\u5bf9\u4e8eBcl-2\u4f9d\u8d56\u7684\u80bf\u7624\u7ec6\u80de\u5177\u6709\u5f3a\u7684\u6297\u80bf\u7624\u6d3b\u6027\uff0c\u5e76\u4e14\u4e0e\u5176\u4ed6\u6297\u764c\u836f\u7269\u7ec4\u5408\u8868\u73b0\u51fa\u66f4\u5e7f\u6cdb\u7684\u6297\u80bf\u7624\u6d3b\u6027\u3002APG-2575\u73b0\u5df2\u83b7\u5f97\u7f8e\u56fd\u3001\u4e2d\u56fd\u3001\u6fb3\u5927\u5229\u4e9a\u3001\u6b27\u6d32\u591a\u9879\u4e34\u5e8a\u8bd5\u9a8c\u8bb8\u53ef\uff0c\u6b63\u5728\u5168\u7403\u540c\u6b65\u63a8\u8fdb\u591a\u4e2a\u8840\u6db2\u80bf\u7624\u9002\u5e94\u75c7\u7684\u4e34\u5e8a\u5f00\u53d1\u3002<\/p>\n

\u7ed3\u5408T-PLL\u53d1\u75c5\u673a\u5236\u53ca\u53ef\u80fd\u7684\u5206\u5b50\u6cbb\u7597\u7a81\u7834\u53e3\uff0c\u57fa\u4e8eAPG-115\u4ee5\u53caAPG-2575\u826f\u597d\u7684\u4e34\u5e8a\u524d\u6570\u636e\u53ca\u65e9\u671f\u4e34\u5e8a\u6570\u636e\uff0c\u4e9a\u76db\u533b\u836fAPG-115\u5355\u836f\u6216\u8054\u5408APG-2575\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbbT-PLL\u60a3\u8005\u7684IIa\u671f\u4e34\u5e8a\u7814\u7a76\u6b64\u524d\u5df2\u83b7\u5f97\u7f8e\u56fdFDA\u4e34\u5e8a\u8bb8\u53ef\u3002<\/p>\n

\u4e9a\u76db\u533b\u836f\u9996\u5e2d\u533b\u5b66\u5b98\u7fdf\u4e00\u5e06\u8868\u793a\uff1a\u201cAPG-2575\u3001APG-115\u90fd\u662f\u4e9a\u76db\u533b\u836f\u7ec6\u80de\u51cb\u4ea1\u4ea7\u54c1\u7ba1\u7ebf\u7684\u91cd\u8981\u54c1\u79cd\uff0c\u6211\u4eec\u975e\u5e38\u671f\u5f85\u4e24\u8005\u8054\u5408\u6cbb\u7597T-PLL\u7684\u4e34\u5e8a\u8bd5\u9a8c\u5c06\u5728\u4e2d\u7f8e\u4e24\u56fd\u542f\u52a8\uff0c\u4e3a\u8be5\u201c\u65e0\u836f\u53ef\u6cbb\u201d\u7684\u4e34\u5e8a\u6076\u6027\u80bf\u7624\u60a3\u8005\u63d0\u4f9b\u66f4\u4e3a\u5b89\u5168\u3001\u9ad8\u6548\u7684\u65b0\u578b\u6cbb\u7597\u836f\u7269\u201d\u3002\u5979\u7279\u522b\u6307\u51fa\uff0c\u201c\u8054\u5408\u7528\u836f\u662f\u80bf\u7624\u6cbb\u7597\u672a\u6765\u53d1\u5c55\u8d8b\u52bf\uff0c\u800cAPG-115\u4e0eAPG-2575\u7684\u8054\u5408\u80fd\u5728\u591a\u79cd\u764c\u75c7\u4e2d\u6fc0\u53d1\u201c\u5408\u6210\u81f4\u6b7b\u201d\u673a\u5236[10<\/span>]<\/sup>\uff0c\u5373\u540c\u65f6\u963b\u65ad\u80bf\u7624\u7ec6\u80de\u501f\u4ee5\u9003\u907f\u7ec6\u80de\u51cb\u4ea1\u7684MDM2-TP53\u53caBCL-2\u4e24\u6761\u5173\u952e\u901a\u8def\uff0c\u4ece\u800c\u5bfc\u81f4\u80bf\u7624\u7ec6\u80de\u65e0\u8def\u53ef\u9003\uff0c\u8fdb\u800c\u6b7b\u4ea1\uff0c\u5177\u6709\u6781\u5927\u7684\u4e34\u5e8a\u610f\u4e49\u3002 \u6b64\u5916\uff0cAPG-115\u53caAPG-2575\u5747\u4e3a\u53e3\u670d\u9776\u5411\u836f\u7269\uff0c\u5b9e\u73b0chemo-free, \u4e34\u5e8a\u5e94\u7528\u4ef7\u503c\u5f88\u9ad8\u3002\u66f4\u91cd\u8981\u7684\u662f\uff0c\u8be5\u8054\u5408\u4e3a\u5168\u7403\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbbT\u5e7c\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\uff08R\/R T-PLL\uff09\u7684\u9996\u521b\u3002\u5e0c\u671b\u6211\u4eec\u7684\u76f8\u5173\u7814\u7a76\u80fd\u66f4\u65e9\u3001\u66f4\u5feb\u8ba9\u66f4\u591a\u60a3\u8005\u53d7\u76ca\u3002\u201d<\/p>\n

\u53c2\u8003\u6587\u732e<\/b><\/p>\n

[1]<\/sup>Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390. <\/p>\n

[2]<\/sup>Matutes E, Brito-Babapulle V, Swansbury J, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood. 1991;78(12):3269-3274. <\/p>\n

[3]<\/sup>Herling M, Khoury JD, Washington LT, Duvic M, Keating MJ, Jones D. A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories. Blood. 2004;104(2):328-335. <\/p>\n

[4]<\/sup>Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D. The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype. J Clin Oncol. 1994;12(12): 2588-2593. <\/p>\n

[5]<\/sup>Herbaux C, Genet P, Bouabdallah K, et al. Bendamustine is effective in T-cell prolymphocytic leukaemia. Br J Haematol. 2015; 168(6):916-919. <\/p>\n

[6]<\/sup>Jain P, Aoki E, Keating M, et al. Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL). Ann Oncol. 2017;28(7):1554-1559. <\/p>\n

[7]<\/sup>Dearden CE, Khot A, Else M, et al. Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route. Blood. 2011;118(22):5799-5802. <\/p>\n

[8]<\/sup>Keating MJ, Cazin B, Coutré S, et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol. 2002;20(1): 205-213. <\/p>\n

[9]<\/sup>Schrader A, Crispatzu G, Oberbeck S, et al. Actionable perturbations of damage responses by TCL1\/ATM and epigenetic lesions form the basis of T-PLL. Nat Commun<\/span>. 2018;9(1):697. <\/p>\n

[10]<\/sup>Pan R, Ruvolo V, Mu H, et al. Synthetic Lethality of Combined Bcl-2 Inhibition and p53 Activation in AML: Mechanisms and Superior Antileukemic Efficacy. Cancer Cell. 2017 Dec 11; 32(6): 748\u2013760.e6.<\/p>\n

\u5173\u4e8e\u4e9a\u76db\u533b\u836f<\/b><\/p>\n

\u4e9a\u76db\u533b\u836f\u662f\u4e00\u5bb6\u7acb\u8db3\u4e2d\u56fd\u3001\u9762\u5411\u5168\u7403\u7684\u5904\u4e8e\u4e34\u5e8a\u5f00\u53d1\u9636\u6bb5\u7684\u539f\u521b\u65b0\u836f\u7814\u53d1\u4f01\u4e1a\uff0c\u81f4\u529b\u4e8e\u5728\u80bf\u7624\u3001\u4e59\u809d\u53ca\u4e0e\u8870\u8001\u76f8\u5173\u7684\u75be\u75c5\u7b49\u6cbb\u7597\u9886\u57df\u5f00\u53d1\u521b\u65b0\u836f\u7269\u30022019\u5e7410\u670828\u65e5\uff0c\u4e9a\u76db\u533b\u836f\u5728\u9999\u6e2f\u8054\u4ea4\u6240\u4e3b\u677f\u6302\u724c\u4e0a\u5e02\uff0c\u80a1\u7968\u4ee3\u7801\uff1a6855.HK\u3002<\/p>\n

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\u524d\u77bb\u6027\u58f0\u660e<\/b><\/p>\n

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 <\/p>\n

<\/div>\n

\u76f8\u5173\u94fe\u63a5 :<\/p>\n

A Leader in the Discovery and Development of Small Molecules that Disrupt Protein-Protein Interactions<\/a><\/p><\/blockquote>\n