Description
CP-547632 is a potent inhibitor of the VEGFR2 and FGF2 kinases with IC50s of 11 and 9 nM, respectively.
Related Catalog
Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR
Research Areas >> Cancer
Target
IC50: 11 nM (VEGFR2), 9 nM (FGF2)[1]
In Vitro
CP-547632 is an ATP-competitive kinase inhibitor that blocks VEGFR-2 kinase autophosphorylation (IC50=11 nM) and VEGF-induced VEGFR-2 phosphorylation in VEGFR-2-transfected endothelial cells (IC50=6 nM). CP-547632 is approximately equipotent (i.e., <10-fold selective) against VEGFR-2, bFGF receptor, and EGFR/Tie-2 chimera, the receptor for Angiopoietin[1].
In Vivo
CP-547632 inhibits tumor-associated VEGFR-2 phosphorylation resulting in decreased microvascular density and significant tumor growth inhibition in a number of tumor models (EC50=590 ng/mL). CP-547632 is shown to inhibit VEGF-induced angiogenesis in vivo in a dose-responsive fashion[1].
Cell Assay
Porcine aortic endothelial cells stably expressing full-length VEGFR-2 have been used. CP-547632 is added to serum-deprived cells and incubated at 37°C, 5% for 1 h. The cells are then stimulated with 500 ng/mL VEGF. Whole cell lysates are then immunoprecipitated using anti-VEGFR-2, and Western blot analysis is carried out with antibodies recognizing either the protein or PY (A) [1].
Animal Admin
Mice[1] MDA-MB-231 cells are injected s.c into the flank of BALB/c male mice. Animals bearing tumors of 75-150 mm3 each are treated with CP-547632 (6.25-100 mg/kg, p.o., qd) in 5% Gelucire. The tumors are measured with calipers, and the tumor volumes are calculated[1].
References
[1]. Beebe JS, et al. Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. Cancer Res. 2003 Nov 1;63(21):7301-9.
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