Discovery of novel EGFR tyrosine kinase inhibitors by structure-based virtual screening

By using of structure-based virtual screening, 13 novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were discovered from 197,116 compounds in the SPECS database here. Among them, 8 compounds significantly inhibited EGFR kinase activity with IC50 values lower than 10 mu M. 3-{[1-(3-Chloro- 4-fluorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}phenyl 2-thiophenecarboxylate (13), particularly, was the most potent inhibitor possessing the IC50 value of 3.5 mu M. The docking studies also provide some useful information that the docking models of the 13 compounds are beneficial to find a new path for designing novel EGFR inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.