|Related VEGFR/PDGFR Inhibitors|
PP121 is a dual inhibitor of tyrosine and phosphoinositide kinases.
DMXAA (Vadimezan, ASA404) is a tumor-vascular disrupting agent (tumor-VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM, respectively.
Ki8751 is a potent, selective inhibitor of VEGFR-2 tyrosine kinase (IC50 = 0.9 nM).
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.
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.