Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116023, China.
Bioorg Med Chem Lett. 2012 Feb 1;22(3):1365-70. doi: 10.1016/j.bmcl.2011.12.067. Epub 2011 Dec 17.
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.
通过基于受体和基于配体的联合虚拟筛选方案，鉴定出 21 种新型化合物，涵盖 15 种骨架，这些化合物被鉴定为 EGFR-T790M/L858R 的新型抑制剂，其中 12 种被鉴定为 EGFR-T790M/L858R 对野生型 EGFR 的选择性抑制剂，5 种对野生型和突变型 EGFR 具有“双重有效”作用。同时，还评估了它们对高表达 EGFR 的人肺癌细胞（A549）、表皮癌细胞（A431）和突变型 EGFR 依赖性细胞（NCI-H1975）的抗增殖作用。
