CP-547632 hydrochloride

CP-547632 hydrochloride is a well-tolerated, orally-bioavailable inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases with IC50s of 11 nM and 9 nM, respectively. CP-547632 hydrochloride is an ATP-competitive kinase inhibitor and it is selective relative to epidermal growth factor receptor, platelet-derived growth factor β, and other related TKs. CP-547632 hydrochloride has antitumor efficacy[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> VEGFR

VEGFR-2:11 nM (IC50)

FGFR:9 nM (IC50)

CP-547632 hydrochloride (1-1000 nM; 1 hours) inhibits VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent fashion, with an IC50 value of 6 nM[1]. Western Blot Analysis[1] Cell Line: Serum-deprived cells Concentration: 1, 4, 16, 63, 250, 1000 nM Incubation Time: 1 hours Result: Inhibited VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent fashion.

CP-547632 hydrochloride (p.o.; 6.25-100 mg/kg/day; for 10-24 days) causes a dose-dependent inhibition of growth in Colo-205, DLD-1, and MDA-MB-231 xenografts[1]. CP-547632 hydrochloride (oral; 50 mg/kg) of a single oral dose of 50 mg/kg yieldes plasma concentrations above 500 ng/ml for 12 hours[1]. Animal Model: Mice bearing tumors (75-150 mm in size)[1] Dosage: 6.25, 12.5, 25, 50, 100 mg/kg Administration: P.o.; daily; 10-24 days Result: Caused a dose-dependent inhibition of growth in Colo-205, DLD-1, and MDA-MB-231 xenografts. Animal Model: H-ras tumor-bearing mice[1] Dosage: 50 mg/kg Administration: Oral Result: A single oral dose of 50 mg/kg yielded plasma concentrations above 500 ng/ml for 12 hours.

[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.