Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors.
Virtual screening was performed to determine potent vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitors. A database of approximately 820,000 commercial compounds was used for screening, and 100 compounds were chosen as candidate VEGFR-2 inhibitors through pharmacophore modeling and docking studies. These 100 compounds were purchased to test their biological activities: 10 compounds were found to inhibit the enzyme, with IC(50) values ranging from 10 to 1 μM. Compound 1, which has a triazinoindole ring, inhibited the enzymatic activity of VEGFR-2, with an IC(50) value of about 1.6 μM, making it the most potent inhibitor of this enzyme. The triazinoindole derivative may therefore serve as the starting point in the design of new VEGFR-2 kinase inhibitors.
Lee
Kyungik
K
Department of Chemistry, Konkuk University, Seoul 143-701, Republic of Korea.
Jeong
Ki-Woong
KW
Lee
Yeonjoo
Y
Song
Ji Yeon
JY
Kim
Maeng Sup
MS
Lee
Gwan Sun
GS
Kim
Yangmee
Y
D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2