文献类型：期刊文献

英文题名：Pyrimido[4,5-d]pyrimidin-4(1H)-one Derivatives as Selective Inhibitors of EGFR Threonine790 to Methionine790 (T790M) Mutants

作者：Xu, Tianfeng[1,2];Zhang, Lianwen[1];Xu, Shilin[1,2];Yang, Chao-Yie[3];Luo, Jinfeng[1];Ding, Fang[1];Lu, Xiaoyun[1];Liu, Yingxue[1];Tu, Zhengchao[1];Li, Shiliang[4];Pei, Duanqing[1];Cai, Qian[1];Li, Honglin[4];Ren, Xiaomei[1];Wang, Shaomeng[3];Ding, Ke[1]

机构：[1]Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Inst Chem Biol, Guangzhou 510530, Guangdong, Peoples R China;[2]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[3]Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA;[4]E China Univ Sci & Technol, Shanghai 200237, Peoples R China

年份：2013

卷号：52

期号：32

起止页码：8387

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20133416652022);WOS:【SCI-EXPANDED(收录号:WOS:000322631600040)】；

基金：We thank National Basic Research Program of China (no 2010CB529706, 2009CB940904), National Natural Science Foundation (no 21072192, 21102146), Key Project on Innovative Drug of Guangdong Province (no 2011A080501013), and Key Project on Innovative Drug of Guangzhou City (no 2009Z1-E911, 2010J-E551) for their financial support.

语种：英文

外文关键词：drug design; inhibitors; selectivity

摘要：Catching the mutants: Pyrimido[4,5-d]pyrimidin-4(1H)-one derivatives (see example) were identified as specific inhibitors of EGFRT790M mutants. The compounds bound with T790M or L858R/T790M mutants with significantly lower Kd values than that with EGFRWT. They also selectively inhibited EGFR signal transduction and proliferation of NSCLC cells harboring EGFRL858R/T790M mutation, but were significantly less potent to cells with EGFRWT. Copyright ? 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.