SU5416 (Semaxanib) is a potent and selective vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 inhibitor that also inhibits other tyrosine kinases KIT, MET, FLT3 and RET. SU5416 inhibited cell migration of human vascular endothelial cells expressing both Flt-1 and KDR in response to VEGF and also inhibited the cell migration in response to placenta growth factor (PIGF), a specific ligand for Flt-1. Chemotaxis of monocytes expressing only Flt-1 was also inhibited by SU5416 in a dose-dependent manner. Moreover, SU5416 was found to inhibit tyrosine kinase of Flt-1 in response to PIGF in vitro. SU5416 efficiently inhibited Kit activity in vivo when administered on a twice-weekly schedule.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points.
O'Donnell A, et al. Br J Cancer. 2005 Oct 17;93(8):876-83. PMID: 16222321.
Antiangiogenic effect by SU5416 is partly attributable to inhibition of Flt-1 receptor signaling.
Itokawa T, et al. Mol Cancer Ther. 2002 Mar;1(5):295-302. PMID: 12489845.
The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function.
Mendel DB, et al. Clin Cancer Res. 2000 Dec;6(12):4848-58. PMID: 11156244.
SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types.
Fong TA, et al. Cancer Res. 1999 Jan 1;59(1):99-106. PMID: 9892193.
|Related VEGFR/PDGFR Products|
Regorafenib is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.
SU4312 is a selective and potent inhibitor of VEGFR and PDGFR tyrosine kinases with IC50 values are 0.8 and 19.4 μM respectively.
Vatalanib is an inhibitor of the VEGFR tyrosine kinases VEGFR-1 (Flt-1, IC₅₀ = 77 nM) and VEGFR-2 (FLK-1/KDR, IC₅₀ = 37 nM), with slightly higher potency against the latter.
ZM323881 is a potent and selective VEGFR2 inhibitor with IC50 of 2 nM and almost has no activity on VEGFR1, PDGFRβ, FGFR1, EGFR and ErbB2.
CEP-11981 is an oral vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor.