Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking.

Article Details

Citation

Copy to clipboard

Du J, Lei B, Qin J, Liu H, Yao X

Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking.

J Mol Graph Model. 2009 Jan;27(5):642-54. doi: 10.1016/j.jmgm.2008.10.006. Epub 2008 Nov 5.

PubMed ID

19081278 [ View in PubMed

]

Abstract

The vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases VEGFR-2 or kinase insert domain receptor (KDR) are attractive targets for the development of novel anticancer agents. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of selective inhibitors of KDR. Docking studies were performed to explore the binding mode between all of the inhibitors and the KDR and produce the bioactive conformation of each compound in the whole dataset. Two conformer-based alignment strategies were employed to construct reliable 3D-QSAR models. The docked conformer-based alignment strategy gave the best 3D-QSAR models. The best CoMFA and CoMSIA models gave a cross-validated coefficient q(2) of 0.546 and 0.715, non-cross-validated r(2) values of 0.936 and 0.961, predicted r(2) values of 0.673 and 0.797, respectively. The information obtained from molecular modeling studies were very helpful to design some novel selective inhibitors of KDR with desired activity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-cyclopropyl-6-[(6,7-dimethoxyquinolin-4-yl)oxy]naphthalene-1-carboxamide	Vascular endothelial growth factor receptor 2	IC 50 (nM)	0.603	N/A	N/A	Details