Pharmacophore modeling and in silico screening for new KDR kinase inhibitors

Hui Yu; Zhanli Wang; Liangren Zhang; Jufeng Zhang; Qian Huang

doi:10.1016/j.bmcl.2007.01.089

Pharmacophore modeling and in silico screening for new KDR kinase inhibitors

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2126-33. doi: 10.1016/j.bmcl.2007.01.089. Epub 2007 Feb 2.

Authors

Hui Yu¹, Zhanli Wang, Liangren Zhang, Jufeng Zhang, Qian Huang

Affiliation

¹ Central Experimental Laboratory, The First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.

PMID: 17306530
DOI: 10.1016/j.bmcl.2007.01.089

Abstract

In order to elucidate the essential structural features for KDR kinase inhibitors, three-dimensional pharmacophore hypotheses were built on the basis of a set of known KDR kinase inhibitors selected from the literature with CATALYST program. Several methods tools used in validation of pharmacophore hypothsis were presented, and the first hypothesis (Hypo1) was considered to be the best pharmacophore hypothesis. The model (Hypo1) was then employed as 3D search query to screen the Traditional Chinese Medicine Database (TCMD) for other potential lead compounds. One hit illustrated high binding affinity with KDR kinase measured by the surface plasmon resonance biosensor. Docking studies may help elucidate the mechanisms of KDR kinase receptor-ligand interactions.

MeSH terms

Computer Simulation*
Databases, Factual
Drug Design
Humans
Inhibitory Concentration 50
Ligands
Models, Molecular
Molecular Structure
Protein Binding
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Quantitative Structure-Activity Relationship*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Ligands
Protein Kinase Inhibitors
Vascular Endothelial Growth Factor Receptor-2