1. Combined SVM-based and docking-based virtual screening for retrieving novel inhibitors of c-Met
- Author
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Xie, Qing-Qing, Zhong, Lei, Pan, You-Li, Wang, Xiao-Yan, Zhou, Jian-Ping, Di-wu, Lei, Huang, Qi, Wang, Yu-Lan, Yang, Ling-Ling, Xie, Huan-Zhang, and Yang, Sheng-Yong
- Subjects
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CARCINOGENESIS , *DRUG resistance in cancer cells , *ANTINEOPLASTIC agents , *SUPPORT vector machines , *ENZYME inhibitors , *MET receptor , *PROTEIN kinases , *GENETIC algorithms - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2011
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