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Eur J Med Chem. 2011 Sep;46(9):3675-80. doi: 10.1016/j.ejmech.2011.05.031. Epub 2011 May 25.

Combined SVM-based and docking-based virtual screening for retrieving novel inhibitors of c-Met.

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1
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.

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.

PMID:
21641696
DOI:
10.1016/j.ejmech.2011.05.031
[Indexed for MEDLINE]
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