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

Article Details

Citation

Xie QQ, Zhong L, Pan YL, Wang XY, Zhou JP, Di-Wu L, Huang Q, Wang YL, Yang LL, Xie HZ, Yang SY

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

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

PubMed ID
21641696 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamideHepatocyte growth factor receptorIC 50 (nM)1.8N/AN/ADetails
1-[(2-NITROPHENYL)SULFONYL]-1H-PYRROLO[3,2-B]PYRIDINE-6-CARBOXAMIDEHepatocyte growth factor receptorIC 50 (nM)82N/AN/ADetails
2-(4-fluorophenyl)-N-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]carbamoyl}acetamideHepatocyte growth factor receptorIC 50 (nM)110N/AN/ADetails
3-[3-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)quinoxalin-5-yl]phenolHepatocyte growth factor receptorIC 50 (nM)900N/AN/ADetails
CrizotinibHepatocyte growth factor receptorIC 50 (nM)4N/AN/ADetails
N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamideHepatocyte growth factor receptorIC 50 (nM)35N/AN/ADetails