Pharmacophore modeling studies of type I and type II kinase inhibitors of Tie2

摘要: In this study, chemical feature based pharmacophore models of type I and II kinase inhibitors Tie2 have been developed with the aid HipHop HypoRefine modules within Catalyst program package. The best model Hypo1_I for contains one hydrogen-bond acceptor, donor, general hydrophobic, hydrophobic aromatic, ring aromatic feature. And Hypo1_II inhibitors, which was characterized by correlation coefficient (0.976032) lowest RMSD (0.74204), consists two donors, features, as well excluded volumes. These validated using either or both test set cross validation methods, shows that a good predictive ability. space arrangements features in are consistent locations three portions making up typical inhibitor, namely, portion occupying ATP binding region (ATP-binding-region portion, AP), (hydrophobic-region HP), linking AP HP (bridge BP). Our study also reveals ATP-binding-region plays an important role to bioactivity inhibitors. Structural modifications on should be helpful further improve inhibitory potency