cp-547632-hydrochloride

Description: CP-547632 HCl (PAN90806), a novel isothiazole, is a orally-bioavailable andATP-competitive inhibitor of the VEGFR-2 and basic fibroblast growthfactor (FGF) kinases with IC50s of 11 nM and 9 nM, respectively. It isselective relative to epidermal growth factor receptor, platelet-derivedgrowth factor beta, and other related TKs. It also inhibitsVEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assaywith an IC(50) value of 6 nM. After oral administration of CP-547, 632 tomice bearing NIH3T3/H-ras tumors, VEGFR-2 phosphorylation in tumors wasinhibited in a dose-dependent fashion (EC(50) = 590 ng/ml). Theseplasma concentrations correlated well with the observed concentrationsof the compound necessary to inhibit VEGF-induced corneal angiogenesisin BALB/c mice. A sponge angiogenesis assay was used to directly comparethe inhibitory activities of CP-547, 632 against FGF receptor 2 orVEGFR-2; this compound potently inhibits both basic FGF and VEGF-inducedangiogenesis in vivo. The antitumor efficacy of this agent wasevaluated after once daily p.o. administration to athymic mice bearinghuman xenografts and resulted in as much as 85% tumor growth inhibition.CP-547, 632 is a well-tolerated, orally-bioavailable inhibitor presentlyunder clinical investigation for the treatment of human malignancies.

References: Cancer Res. 2003 Nov 1; 63(21):7301-9.

Related CAS: 252003-71-7 (HCl salt); 252003-65-9 (free base)