title: Combined SVM-based and docking-based virtual screening for retrieving novel inhibitors of c-Met.
abstract: Aberrant c-Met activation has been demonstrated to be implicated in tumorigenesis and anti-cancer drug resistance. Discovery of c-Met inhibitors has attracted much attention in recent years. In this study, a support vector machine (SVM) classification model that discriminates c-Met inhibitors and non-inhibitors was first developed. Evaluation through screening a test set indicates that combined SVM-based and docking-based virtual screening (SB/DB-VS) considerably increases hit rate and enrichment factor compared with the individual methods. Thus the combined SB/DB-VS approach was adopted to screen PubChem, Specs, and Enamine for c-Met inhibitors. 75 compounds were selected for in vitro assays. Eight compounds display a good inhibitory potency against c-Met. Five of them are found to have novel scaffolds, implying a good potential for further chemical modification.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, No 1, Keyuan 4 Road, High Tech Park, Chengdu, Sichuan 610041, China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Xie
authors.forename: Lei
authors.initials: L
authors.lastname: Zhong
authors.forename: You-Li
authors.initials: YL
authors.lastname: Pan
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Di-Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Wang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Yang
authors.forename: Huan-Zhang
authors.initials: HZ
authors.lastname: Xie
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D019859:Proto-Oncogene Proteins c-met