title: A combination of 2D similarity search, pharmacophore, and molecular docking techniques for the identification of vascular endothelial growth factor receptor-2 inhibitors.
abstract: The human vascular endothelial growth factor receptor-2 (VEGFR-2) has been an attractive target for the inhibition of angiogenesis. In the current study, we used a hybrid protocol of virtual screening methods to retrieve new VEGFR-2 inhibitors from the Zinc-Specs Database (441 574 compounds). The hybrid protocol included the initial screening of candidates by comparing the 2D similarity to five reported top active inhibitors of 13 VEGFR-2 X-ray crystallography structures, followed by the pharmacophore modeling of virtual screening on the basis of receptor-ligand interactions and further narrowing by LibDOCK to obtain the final hits. Two compounds (AN-919/41439526 and AK-968/40939851) with a high libscore were selected as the final hits for a subsequent cell cytotoxicity study. The two compounds screened exerted significant inhibitory effects on the proliferation of cancer cells (U87 and MCF-7). The results indicated that the hybrid procedure is an effective approach for screening specific receptor inhibitors.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, Department of Biomedical Engineering, China Pharmaceutical University, Nanjing, China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Ai
authors.forename: Caiping
authors.initials: C
authors.lastname: Tian
authors.forename: Dawei
authors.initials: D
authors.lastname: Deng
authors.forename: Guissi
authors.initials: G
authors.lastname: Fida
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D062126:Databases, Chemical; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2