CP-724,714 is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 10 nM and also inhibits EGFR with IC50 of 6.4 μM.
cp-724714 is an inhibitor of erbb2 and egfr kinases with ic50 values of 10±3 nmol/l and 6,400±2,100 nmol/l, respectively [1].in the in vitro cell cycle assay, cp-724714 cause a g1 block of the her2-amplified bt-474 breast cancer cells due to its inhibition of erbb2. cp-724714 at 1 mol/l can also reduce the level of phospho-erbb2 in these cells. in in vivo assay, cp-724714 cause a concentration-dependent reduction of tumor erbb2 receptor phosphorylation in athymic mice bearing fre-erbb2xenografts. cp-724714 treatments also resulted in a time- and dose-dependent induction of tumor cell apoptosis. in two human breast carcinoma models, bt-474 and mda-mb-453, which are her2 amplified and highly overexpress erbb2, cp-724714 is found to produce a dose-dependent inhibition of xenograft growth. in addition, cp-724,714 treatments induce reduction of downstream erbb2 rtk signaling. on the basis of these, cp-724,714 was advanced to phase i clinical trials and is potentially another option for her2-driven breast cancer [1].
[1] jitesh p. jani, richard s. finn, mary campbell, et al. discovery and pharmacologic characterization of cp-724714, a selective erbb2 tyrosine kinase inhibitor. cancer research. 2007 (67): 9887-9893.
