2-甲氧基-N-[(2E)-3-[4-[[3-甲基-4-[(6-甲基-3-吡啶基)氧基]苯基]氨基]-6-喹唑啉基]-2-丙烯-1-基]乙酰胺

溶解度:Soluble to 10 mM in DMSO

生物活性

CP-724,714 is an orally available, small molecule, potent HER-2 tyrosine kinase inhibitor under development for the treatment of advanced HER2-overexpressing cancers. It inhibits HER2-chimera phosphorylation with an IC50 of 15 ng/ml (32 nM), and is��500-fold selective for HER2 relative to other kinases (e.g. EGFR, PDGFR, IGF-1R, VEGFR-2, abl, src). Antitumor activity of CP-724,714 was observed in murine xenografts of human adenocarcinomas of breast (BT-474 and MDAMB-453), pancreas (Panc-1), lung (Calu-3), and ovary (SKOV-3).Aditionally, CP-724,714 showed a favorable nonclinical toxicity profile with no apparent effects on cardiac tissue. On the basis of these promising preclinical results, CP-724,714 was advanced to phase I clinical trials and is potentially another option for women with Her2-driven breast cancer.

参考文献

JP Jani et al. Discovery and Pharmacologic Characterization of CP-724,714, a Selective ErbB2 Tyrosine Kinase Inhibitor. Cancer Res. 2007, 67(20), 9887-9893. PN Munster et al. First Study of the Safety, Tolerability, and Pharmacokinetics of CP-724,714 in Patients with Advanced Malignant Solid HER2-Expressing Tumors. Clin. Cancer Res. 2007, 13, 1238-1245.