Endoxifen (E-isomer hydrochloride) is a tamoxifen metabolite and potent Selective Estrogen Response Modifier (SERM). Target: Estrogen Receptor/ERREndoxifen is considered a prodrug, since it has a much higher potency for the estrogen receptor than its parent drug. Endoxifen inhibits the hERG channel protein trafficking to the plasma membrane in a concentration-dependent manner with Endoxifen being more potent than Tamoxifen. [1] Endoxifen is also shown to be a more potent inhibitor of estrogen target genes when ERβ is expressed. Additionally, low concentrations of Endoxifen observed in Tamoxifen treated patients with deficient CYP2D6 activity (20 to 40 nM) markedly inhibit estrogen-induced cell proliferation rates in the presence of ERβ, whereas much higher Endoxifen concentrations are needed when ERβ is absent.[2]
[1]. Chae YJ, et al. Endoxifen, the active metabolite of tamoxifen, inhibits cloned hERG potassium channels. Eur J Pharmacol. 2015 Apr 5;752:1-7. [2]. Wu X, et al. Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen. Breast Cancer Res. 2011 Mar 10;13(2):R27.