Endoxifen (Z-isomer hydrochloride)

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