title: Discovery of novel EGFR tyrosine kinase inhibitors by structure-based virtual screening.
abstract: 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 IC(50) values lower than 10 μM. 3-{[1-(3-Chloro-4-fluorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}phenyl 2-thiophenecarboxylate (13), particularly, was the most potent inhibitor possessing the IC(50) value of 3.5 μM. 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.
authors.affiliation: Shanghai Key Laboratory of Functional Materials Chemistry, and Research Centre of Analysis and Test, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.forename: Xianqiang
authors.initials: X
authors.lastname: Sun
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.forename: Minbo
authors.initials: M
authors.lastname: Lan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D016208:Databases, Factual; D055808:Drug Discovery; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors