ChemicalBook CAS DataBase List 252003-71-7

252003-71-7

Name	CP-547632 (hydrochloride)
CAS	252003-71-7
Molecular Formula	C20H25BrClF2N5O3S
MDL Number	MFCD20268381
Molecular Weight	568.86
MOL File	252003-71-7.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	DMSO: 38.33 mg/mL (67.38 mM); Water: < 0.1 mg/mL (insoluble)
form	Solid
color	White to light yellow
InChIKey	NNPJZJJMQDXYGN-UHFFFAOYSA-N
SMILES	NC(C1=C(NC(NCCCCN2CCCC2)=O)SN=C1OCC3=C(F)C=C(Br)C=C3F)=O.[H]Cl

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H315-H319-H335
Precautionary statements	P305+P351+P338
WGK Germany	WGK 3
Storage Class	11 - Combustible Solids
Hazard Classifications	Eye Irrit. 2 Skin Irrit. 2 STOT SE 3

Hazard Information

Uses

CP-547632 hydrochloride is an orally active, ATP-competitive and potent VEGFR-2 and FGF kinases inhibitor with IC50s of 11 nM and 9 nM, respectively. CP-547632 hydrochloride is selective for VEGFR2 and bFGF over EGFR, PDGFRβ, and related tyrosine kinases (TKs). CP-547632 hydrochloride has antitumor efficacy[1].

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 )

IC 50

VEGFR-2: 11 nM (IC₅₀); FGFR: 9 nM (IC₅₀)

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. PMID:14612527

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