Discovery of novel selective inhibitors for EGFR-T790M/L858R.
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.
Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116023, China.
Fang
F
Bai
Hongyan
H
Liu
Linjiang
L
Tong
Wei
W
Zhou
Li
L
Liu
Zhenjiang
Z
Zhao
Xiaofeng
X
Liu
Hualiang
H
Jiang
Xicheng
X
Wang
Hua
H
Xie
Honglin
H
Li
D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors