CP-724714 is a potent, selective HER2/ErbB2 inhibitor with an IC50 of 10 nM, more than 640 times more selective in cell-free trials than for EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, c-Met, and others. Phase 2.

 

Brand: BCM

 

Target: HER2/ErbB2

 

In Vitro: Cp-724,714 selectively acted on EGFR with IC50 of 6.4 μM. Cp-724,714 is more than 1000 times less effective on IR,IGF-1R,PDGFRβ,VGFR2,Abl, Src,c-Met, c-jun NH2-terminal kinase (JNK)-2,JNK-3,ZAP-70, cyclin-dependent kinase (Cdk)-2, and CDK-5. Cp-724,714 effectively reduced EGF-induced autophosphorylation in chimeras containing the erbB2 kinase domain with an IC50 of 32 nM, but the effect on NIH3T3 cells transfected with EGFR was significantly lower. CP-724,714 inhibited the proliferation of ERBB2-enhanced cells, including BT-474 and SKBR3, with IC50 of 0.25 and 0.95 μM, respectively. 1 μM CP-724,714 acted on BT-474 cells and induced cell accumulation in G1 phase, but decreased significantly in S phase. CP-724,714 may exhibit hepatotoxicity through mechanisms of hepatocellular injury and cholestasis. CP-724,714 inhibits the entry of TC into membrane vesicles expressing the human bile salt output pump with an IC50 of 16 μM, and inhibits major efflux transport of MDR1 in the timid duct with an IC50 of ~28 μM.

 

In Vivo: Cp-724,714 was orally treated with 25 mg/kg dose of FE-ERBB2 and BT-474 in transplanted tumors, which was rapidly absorbed and caused a decrease in tumor erbB2 receptor phosphorylation. CP-724,714 induced apoptosis in mice transplanted with subcutaneous injection of FE-ERBB2, and 50 mg/kg showed tumor growth inhibition of up to 50% without weight loss or death. Cp-724,714 has strong anticancer activity against transplanted tumors of MDA-MB-453,MDA-MB-231,LoVo(colon), and Colo-205(colon). Furthermore,CP-724,714 treated BT-474 grafts at doses of 30 or 100 mg/kg, reducing extracellular signal-regulated kinase and Akt phosphorylation.

 

Solubility: Soluble in DMSO; soluble in Ethanol. Insoluble in Water.

 

Attribute
[Chem Name]	2-Methoxy-N-[3-[4-[[3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl]amino]quinazolin-6-yl]allyl]acetamide
[Synonym]	CP-724714
[CAS No.]	537705-08-1
[MDL No.]	MFCD19687281
[Formula]	C27H27N5O3
[Molecular]	469.54
[Form]	Solid Powder
[Storage]	Sealed in dry, 2-8°C

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