Background:

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-erbB2

Xenografts. 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].

参考文献:
[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.