Construction of 3D pharmacophore model of vascular endothelial growth factor receptor 2 inhibitors / 第二军医大学学报

ABSTRACT

Objective To construct the three dimensional pharmacophore models of inhibitors of vascular endothelial growth factor receptor 2 (VEGFR-2), so as to provide a theoretical model for designing novel VEGFR-2 inhibitors. Methods The model was derived from 30 reported VEGFR-2 inhibitors (21 molecules as training set and the rest as testing set) with structural variety and resembling binding mode, whose IC50 values spanned 5 magnitudes by using Catalyst Software in Discovery Studio 2. 5 Package. Results The best model consists of one hydrogen bond receptor, two hydrophobic cores, one aromatic plane and 4 excluded volumes. The predictive relativity (i?) was 0. 89. Conclusion Cross-validation results indicate that the constructed model has satisfactory predictivity and can be used to screen molecule databases for searching novel lead compounds which can inhibit VEGFR-2.