CP-724714 is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 10 nM, > 640-fold selectivity against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, c-Met etc.
Human epidermal growth factor receptor (EGFR; HER1,erbB1), human epidermal growth factor r eceptor 2 (HER2; erbB2), HER3 (erbB3) and HER4 (erbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. Among them, HER2 is a validated and high-value target. Approximately 30% of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product, HER2. Also, overexpression of HER2 occurs in gastric, colorectal, NSCLC and ovarian cancers. CP-724714 is a potent inhibitor of HER2 with IC50 value of 10nM (measured by kinase activity), ~640-fold selectivity for HER2 than the closely related kinase EGFR. NIH 3T3 cells transfected with chimeric EGFR/HER2 exposure to CP-724714>250nM showed decrease of EGF-induced autophosphorylation level of HER2. Colony formation was reduced by >80% by CP-724714 at concentration of 1μM in BT-474 cells and at 3μM in SKBR3 cells. Accumulation in G1 phase and a marked reduction in S-phase can be observed in BT-474 cells treated with 1μM CP-724714 for 24h. Oral administration of CP-724714 at dose ranging in 6.25-100mg/kg, q.d., resulted in dose-dependent inhibition of FRE-erbB2 xenografts and 50% tumor growth inhibition at 50mg/kg. Tumor growth inhibition by 41%, 42%, 81% and 100% achieved by 1, 10, 30, and 100 mg/kg CP-724714 in BT-474 xenografts. Also, the tumor growth inhibition of MDA-MB-453 xenografts by 19%, 66%, and 83% was achieved in the 25, 50 and 100 mg/kg b.i.d. treatment groups, respectively. Meanwhile, the reduction ranging in 69%-79% of HER2 phosphorylation in these groups treated with CP-724714 can be observed. Also, treatment with CP-724714 at 30mg/kg or 100mg/kg resulted in significant reduction of p-ERK and p-ATK, the downstreams activated by HER2, in BT-474 xenografts[1].
CP-724714 动物研究
Dose
Mice[1] (p.o.): min = 3.125 mg/kg, max = 100 mg/kg
Administration
p.o.
CP-724714 实验方案
计算器
存储液制备
1mg
5mg
10mg
1 mM
5 mM
10 mM
2.13mL
0.43mL
0.21mL
10.65mL
2.13mL
1.06mL
21.30mL
4.26mL
2.13mL
CP-724714 技术信息
CAS号
383432-38-0
分子式
C27H27N5O3
分子量
469.535
别名
运输
蓝冰
存储条件
液体-20°C:3-6个月-80°C:12个月
粉末Keep in dark place,Sealed in dry,Room Temperature
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