Endoxifen (Z-isomer)

Endoxifen Z-isomer hydrochloride, an orally active Tamoxifen (HY-13757A) metabolite, is a selective estrogen receptor modulator with 100-fold more potency than its parent agent, Tamoxifen. Endoxifen Z-isomer inhibits PKCβ1 kinase activity. Endoxifen Z-isomer attenuates PKCβ1-activated AKT^Ser473 phosphorylation, diminishes AKT substrate phosphorylation, and induces Apoptosis. Endoxifen Z-isomer exhibits anticancer activity against hormone-resistant metastatic breast cancer^[1][2][3][4]. In Vitro:Endoxifen Z-isomer (2.5-10  µM; 48  h) inhibits growth and induces apoptosis in estrogen deprived ERα⁺ /HER2^- MCF7AC1 cells^[2].
Endoxifen Z-isomer (0.1-5 μM, 7 days) exhibits potent antiproliferative activity against MCF7AC1 and MCF7LR cell lines^[4].
In Vivo:Z-Endoxifen (Z-isomer) (5 mg/kg/day, s.c., gradual drug release every 30 days, pellets replaced every 90 days) effectively prevents breast cancer in the C3(1)-TAg mouse model^[3].
Z-Endoxifen (50 mg/kg, p.o., 5 times a week for 4 weeks) shows better antitumor efficacy in the MCF7LR resistant mouse model^[4].
Z-Endoxifen (75 mg/kg, p.o., once daily for 4 weeks) shows strong antitumor activity in the MCF7AC1 mouse breast cancer model^[4].