Description
Vatalanib is an antagonist of the VEGF receptors, inhibiting the receptor tyrosine kinase activities of VEGFR1 (Flt1), VEGFR2 (KDR), and VEGFR3 (Flt4) with IC
50 values of 77, 37, and 190 nM, respectively. It less potently inhibits PDGF and c-
Kit (IC
50 = 600 and 700 nM) and has no effect on a large panel of additional kinases. Vatalanib completely blocks retinal neovascularization in oxygen-
induced ischemic retinopathy in mice, suggesting its use in diabetic retinopathy and other diseases featuring aberrant vascular development.
Chemical Properties
White to Off-White Crystalline Powder
Uses
Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. Antineoplastic.
Uses
Vatalanib (PTK787) is an inhibitor of VEGFR2/KDR, Flt-1 and c-Kit with IC50 of 37 nM, 77 nM and 730 nM, respectively.
in vivo
Vatalanib induces dose-dependent inhibition of the angiogenic response to VEGF and PDGF in both a growth factor implant model and a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, Vatalanib also inhibits the growth and metastasesof several human carcinomas in nude mice without significant effect on circulating blood cells or bone marrow leukocytes[1].
IC 50
VEGFR2: 37 nM (IC
50)
References
1) Wood?et al. (2000),?PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration;? Cancer Res.,?60?2178
2) Lin?et al. (2002),?The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in bone marrow microenvironment;? Cancer Res.,?62?5019
