CP-547632

Names

[ CAS No. ]:
252003-65-9

[ Name ]:
CP-547632

[Synonym ]:
3-(4-Bromo-phenoxymethyl)-benzoic acid
3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide
3-(4-bromo-2,6-difluorobenzyloxy)-5-(3-(4-pyrrolidin-1-ylbutyl)ureido)isothiazole-4-carboxylic acid amide
3-[(4-Bromo-2,6-difluorobenzyl)oxy]-5-({[4-(1-pyrrolidinyl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide
3-[(4-bromo-2,6-difluorobenzyl)oxy]-5-({[4-(pyrrolidin-1-yl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide
3-(4-Brom-benzyloxy)-benzoesaeure
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-[[[[4-(1-pyrrolidinyl)butyl]amino]carbonyl]amino]-4-isothiazolecarboxamide
CP-547632
4-Isothiazolecarboxamide, 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-[[[[4-(1-pyrrolidinyl)butyl]amino]carbonyl]amino]-
3-(4-bromo-benzyloxy)-benzoic acid

Biological Activity

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
548.6±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₀H₂₄BrF₂N₅O₃S

[ Molecular Weight ]:
532.402

[ Flash Point ]:
285.6±30.1 °C

[ Exact Mass ]:
531.075134

[ PSA ]:
137.82000

[ LogP ]:
3.69

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.622

Safety Information

[ HS Code ]:
2934999090

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%