期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 46, 期 9, 页码 3675-3680出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2011.05.031
关键词
c-Met inhibitor; Drug discovery; Molecular docking; Support vector machine; Virtual screening
资金
- National ST Major Project [2009ZX09501-001, 2009ZX09103-133]
- National Natural Science Foundation of China [20872100]
- Ph.D. Programs Foundation of Ministry of Education of China [20100181110025]
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. (C) 2011 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据