Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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3D-QSAR Studies of VEGFR-2 Kinase Inhibitors Based on Docking

Author(s): Xiaoping Jiang, Guangchuan Ou, Depeng Yan, Min Zhang, Xianyou Yuan.

Abstract:

The growth and metastasis of solid tumors are dependent on angiogenesis. The vascular endothelial growth factor (VEGF) is of particular interest since it is essential for angiogenesis. The development of novel inhibitors of VEGF receptor type 2 (VEGFR-2) is important. Quantitative structure – activity relationship (QSAR) studies were performed to understand the structural factors affecting inhibitory potency of 4-aryl-5-cyano-2-aminopyrimidines. Docking studies were performed to explore the binding mode between all of the inhibitors and the VEGFR-2 and produce the bioactive conformation of each compound in the whole dataset. The docked conformer-based alignment strategy gave the 3DQSAR models. Both CoMFA (q2= 0.575, r2 = 0.903, and r2predictive = 0.763) and CoMSIA (q2 = 0.617, r2 = 0.869, and r2predictive = 0.783) gave reasonable results. The contour maps obtained from 3D-QSAR studies were evaluated for activity trends for the molecules analyzed. CoMSIA models exhibited good external predictivity as compared with that of CoMFA models. The data generated from the present study helped us to predict the activity of new inhibitors and further design some novel and potent VEGFR-2 enzyme inhibitors.

Keywords: VEGFR-2, QSAR, CoMFA, CoMSIA, Docking, Molecules Models, 3D-QSAR, Angiogenesis, angiopoietins, endothelial cells, IC50 values, Redhat Linux WS 5.3, SYBYL, DOCK6.0, PLS Regression Analysis, ligand orientations, little caves

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Article Details

VOLUME: 8
ISSUE: 10
Year: 2011
Page: [926 - 942]
Pages: 17
DOI: 10.2174/157018011797655296
Price: $58