Endoxifen HCl, the active metabolite of Tamoxifen, ia a potent and selective estrogen receptor antagonist. Phase 2.
Endoxifen shows anti-estrogenic effects, and decreases the E2-induced PR expression in MCF-7 cells. [1] Endoxifen also blocks ER-alpha transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation. [2] In MCF7, HS 578T, and BT-549 cells, Endoxifen significantly inhibits cell proliferation. [3] Endoxifen also exhibits four-fold higher inhibition on PKC activity compared to tamoxifen. [4] Endoxifen inhibits the hERG current by preferentially interacting with the activated states of cloned hERG potassium channels with IC50 of 1.6 μM. [5]
In vivo, Endoxifen (8 mg/kg, ) inhibits growth of MCF-7 human mammary tumor xenografts in mice, showing more potency than Tamoxifen. [3]
[1] Lim YC, et al. Cancer Chemother Pharmacol. 2005, 55(5), 471-478. [2] Wu X, et al. Cancer Res. 2009, 69(5), 1722-1727. [3] Ahmad A, et al. Breast Cancer Res Treat. 2010, 122(2), 579-584.