文献类型：期刊文献

英文题名：Discovery of novel selective inhibitors for EGFR-T790M/L858R

作者：Bai, Fang[1,2];Liu, Hongyan[3];Tong, Linjiang[3];Zhou, Wei[4,5];Liu, Li[4,5];Zhao, Zhenjiang[4,5];Liu, Xiaofeng[4,5];Jiang, Hualiang[4,5,6];Wang, Xicheng[1];Xie, Hua[3];Li, Honglin[4,5]

机构：[1]Dalian Univ Technol, Dept Engn Mech, State Key Lab Struct Anal Ind Equipment, Dalian 116023, Peoples R China;[2]Dalian Univ Technol, Fac Chem Environm & Biol Sci & Technol, Dalian 116023, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;[4]E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[6]Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China

年份：2012

卷号：22

期号：3

起止页码：1365

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000300404200014)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants 20803022 21173076, and 81102375), the Special Fund for Major State Basic Research Project (Grant 2009CB918501), the Shanghai Committee of Science and Technology (Grants 09dZ1975700 and 10431902600), and the National S&T Major Project of China (Grant 2011ZX09307-002-03). Honglin Li is also sponsored by Shanghai Rising-Star Program (Grant 10QA1401800) and Program for New Century Excellent Talents in University (Grant NCET-10-0378).

语种：英文

外文关键词：EGFR; T790M/L858R; Virtual screening; Kinase inhibitors; Selective inhibitors; Dual-effective inhibitors

摘要：Through a receptor-based and ligand-based combined virtual screening protocol, 21 novel compounds covering 15 scaffolds were identified as novel inhibitors for EGFR-T790M/L858R, among which, 12 of them were identified as selective inhibitors for EGFR-T790M/L858R to wild-type EGFR, and 5 of them exhibited 'dual-effective' to wild-type and mutant EGFR. Meanwhile, their antiproliferative effects toward EGFR high-expressing human lung cancer cell (A549), epidermoid carcinoma cell (A431), and the mutant EGFR-dependent cell (NCI-H1975) were also evaluated. (C) 2011 Elsevier Ltd. All rights reserved.