Synthesis of a novel biotin-tagged photoaffinity probe for VEGF receptor tyrosine kinases.
A novel biotin-tagged photoaffinity probe was synthesized and evaluated as a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor. The probe (2) is a potent VEGFR-2 inhibitor with an IC(50) value of 7.1 microM, and inhibits VEGF-induced proliferation in human umbilical vein endothelial cells (HUVEC), with an IC(50) value of 40.3 microM. This probe will be a useful reagent for investigating ligand-protein interactions.
Han
Sun-Young
SY
Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
Park
Seok-Soon
SS
Lee
Woo Ghil
WG
Min
Yong Ki
YK
Kim
Bum Tae
BT
D001710:Biotin / Q000737:chemistry*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008024:Ligands; D008027:Light; D008956:Models, Chemical; D011485:Protein Binding; D011799:Quinazolines / Q000737:chemistry; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
C508739:2,4-dibromo-5-hydroxymethylthiazole; D006842:Hydrocarbons, Brominated; D008024:Ligands; D011799:Quinazolines; D013844:Thiazoles; D001710:Biotin; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2