CP-547632 (hydrochloride)

Biological Activity

CP-547632 hydrochloride is an orally active, ATP-competitive VEGFR-2 and FGF kinase inhibitor with IC50 of 11 nM and 9 nM, respectively. It is selective for VEGFR2 and bFGF over EGFR, PDGFRβ and related tyrosine kinases (TKs), and has an antitumor effects.

in vitro

CP-547632 hydrochloride (1-1000 nM; 1 hour) inhibits VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent fashion, with an IC ₅₀ value of 6 nM.

Western Blot Analysis

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.

in vivo

CP-547632 hydrochloride (po; 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.
CP-547632 hydrochloride (oral; 50 mg/kg; a single oral dose) yieldes plasma concentrations above 500 ng/ml for 12 hours.

Animal Model:	Mice bearing tumors (75-150 mm in size)
Dosage:	6.25, 12.5, 25, 50, 100 mg/kg
Administration:	Po; daily; 10-24 days
Result:	Caused a dose-dependent inhibition of growth in Colo-205, DLD-1, and MDA-MB-231 xenografts.

< td class="col2"> H-ras tumor-bearing mice

Animal Model:
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.

target

VEGFR-2 < span> 11 nM (IC 50 )

FGFR 9 nM (IC 50 )

Raw materials

Preparation Products