Pharmacophore modeling and in silico screening for new KDR kinase inhibitors.
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.
Yu
Hui
H
Central Experimental Laboratory, The First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
Wang
Zhanli
Z
Zhang
Liangren
L
Zhang
Jufeng
J
Huang
Qian
Q
D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D008024:Ligands; D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2