BMS-599626 Hydrochloride (AC480 Hydrochloride) 是一种选择性的口服生物可利用的 HER1 和 HER2 抑制剂，IC50 分别为 20 和 30 nM。 BMS-599626 Hydrochloride 对 HER4 (IC50=190 nM) 的效力降低约 8 倍，对 VEGFR2、c-Kit、Lck、MEK 的效力超过 100 倍。 BMS-599626 Hydrochloride 抑制肿瘤细胞增殖，并有可能增加肿瘤对放疗的反应。
BMS-599626 is a selective inhibitor of HER1 and HER2 with IC50 value of 22 nM and 32 nM, respectively [1].
HER (human epidermal growth factor receptor) is a member of EGFR/ErbB family and plays an important role in transduction of cell proliferation and differentiation. It has been reported that abbrent expression of HER is correlated with cancer and HER inhibition is being regarded as a promising strategy for cancer treatment [1].
BMS-599626 is a potent HER inhibitor and has the higher inhibition ability than the other reported inhibitors. When tested with breast tumor cell lines (HCC202, HCC1942 and AU565) that highly expressing HER1 and HER2, BMS-599626 treatment inhibited cell proliferation, while had no effect on A2780 cells that without HER1 or HER2 expression [1]. Treated OV202 cells with BMS-599626 significantly inhibited cell proliferation and enhanced cell apoptosis by inhibiting HER [2].
In mouse model with Sal2 tumor cells xenograft, oral administration of BMS-599626 inhibited Sal2 cells growth in a dose-dependent manner and significantly delayed tumor growth at the concentration of 60 mg/kg [1].
When tested with Sal2 cells expressing CD8-HER2 fusion protein, BMS-599626 treatment inhibited the receptor phosphorylation and MAPK phosphorylation with the IC50 value of 0.3 and 0.22 μM/L, respectively [1].
参考文献:
[1].Wong, T.W., et al., Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin Cancer Res, 2006. 12(20 Pt 1): p. 6186-93.
[2].Haluska, P., et al., HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924. Mol Cancer Ther, 2008. 7(9): p. 2589-98.
动态评分
0.0