Description
(E)-4-Hydroxytamoxifen is the less active isomer of 4-hydroxytamoxifen. 4-Hydroxytamoxifen is the active metabolite of tamoxifen, a selective estrogen receptor modulator (SERM) that acts as an agonist or antagonist in various tissues. 4-Hydroxytamoxifen exhibits anticancer chemotherapeutic activity, inducing autophagy and vacuole formation as well as KRAS degradation in various cancer cell lines. In cardiac myocytes, 4-hydroxytamoxifen decreases Ca2+ amplitude, slowing relaxation and decreasing contractility.
References
Asp ML, Martindale JJ, Metzger JM. Direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling. PLoS One. 2013 Oct 24;8(10):e78768. PMID: 24205315.
Kohli L, Kaza N, Coric T, et al. 4-Hydroxytamoxifen induces autophagic death through K-Ras degradation. Cancer Res. 2013 Jul 15;73(14):4395-405. PMID: 23722551.
Schwartz JA, Zhong L, Deighton-Collins S, et al. Mutations targeted to a predicted helix in the extreme carboxyl-terminal region of the human estrogen receptor-alpha alter its response to estradiol and 4-hydroxytamoxifen. J Biol Chem. 2002 Apr 12;277(15):13202-9. Erratum in: J Biol Chem 2002 Jul 5;277(27):24842. PMID: 11823467.
