(E/Z)-Endoxifen (Synonyms: (E/Z)-N-desmethyl-4-hydroxy Tamoxifen) |
カタログ番号GC40833 |
(E/Z)-エンドキシフェンは、CYP2D6を含むサイトクロムP450(CYP)アイソフォームの連続的な作用によって生成されるタモキシフェンの有効代謝物質です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 110025-28-0
Sample solution is provided at 25 µL, 10mM.
Endoxifen is a key active metabolite of tamoxifen (TAM) with higher affinity and specificity to estrogen receptor that also inhibits aromatase activity.
Endoxifen, a hydroxylated tamoxifen metabolite, is approximately 100-fold more potent as an antagonist of the ER than tamoxifen. It also suggests that endoxifen but not 4-hydroxytamoxifen results in ER-alpha degradation in addition to its effects on the ER at the level of transcription[1]. Endoxifen, is a potent antiestrogen that targets estrogen receptor α for degradation in breast cancer cells. Additionally, it is showed that Endoxifen blocks ERA transcriptional activity and inhibits estrogen-induced breast cancer cell proliferation even in the presence of tamoxifen, N-desmethyl-tamoxifen, and 4-hydroxytamoxifen[2]. Endoxifen is strongly growth inhibitory at 10 μM for all the breast cancer cell lines except for moderate inhibition for MDAMB-468.Cytotoxic effects are quite significant at 10 μM concentration for MCF7, HS 578T, and BT-549 cells. At lower Endoxifen concentrations (0.01-1 μM), the inhibitory effects are not as significant as 10 μM, whereas 100 μM Endoxifen concentration found to be lethal for all tested cells[3].
Orally administered Endoxifen is rapidly absorbed and systemically available when tested in female rats. The Endoxifen-treated rats show 787% higher exposure (AUC0–∞) and 1,500% higher concentration (Cmax) levels of Endoxifen when compared with Tamoxifen. Oral Endoxifen administration once a day for 28 consecutive days at dosages 2, 4, and 8 mg/kg proves safe and results in progressive inhibition of the growth of the human mammary tumor xenografts in female mice[3].
References:
[1]. Goetz MP, et al. Tamoxifen, endoxifen, and CYP2D6: the rules for evaluating a predictive factor. Oncology (Williston Park). 2009 Dec;23(14):1233-4, 1236.
[2]. Wu X, et al. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res. 2009 Mar 1;69(5):1722-7.
[3]. Wu X, et al. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res. 2009 Mar 1;69(5):1722-7.
Average Rating: 5
(Based on Reviews and 6 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *