Discovery of novel selective inhibitors for EGFR-T790M/L858R

Fang Bai; Hongyan Liu; Linjiang Tong; Wei Zhou; Li Liu; Zhenjiang Zhao; Xiaofeng Liu; Hualiang Jiang; Xicheng Wang; Hua Xie; Honglin Li

doi:10.1016/j.bmcl.2011.12.067

Discovery of novel selective inhibitors for EGFR-T790M/L858R

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1365-70. doi: 10.1016/j.bmcl.2011.12.067. Epub 2011 Dec 17.

Authors

Fang Bai¹, Hongyan Liu, Linjiang Tong, Wei Zhou, Li Liu, Zhenjiang Zhao, Xiaofeng Liu, Hualiang Jiang, Xicheng Wang, Hua Xie, Honglin Li

Affiliation

¹ Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116023, China.

PMID: 22227214
DOI: 10.1016/j.bmcl.2011.12.067

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalytic Domain
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Discovery*
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / genetics
Humans
Inhibitory Concentration 50
Models, Molecular*
Molecular Structure
Mutation
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*

Substances

Protein Kinase Inhibitors
ErbB Receptors