Background:

IC50: 27 and 18 μM for MCF-7 and MDA-MB-231 cell proliferation

4-Hydroxytamoxifen is an estrogen receptor modulator.

Estrogen receptor can be selectively stimulated or inhibited, providing promising therapeutic opportunities for auto-immune diseases, prostate and breast cancer, as well as depression.

In vitro: Previous study was conducted to evaluate the effects of tamoxifen and its active metabolite 4-hydroxytamoxifen on isolated rat cardiac myocyte mechanical function and calcium handling. Results showed that myocytes treated with 4-hydroxytamoxifen had similarly to tamoxifen-treated cells to both calcium handling and contractility [1].

In vivo: Previous animal study compared the extent of DNA adduct formation in SD rats treated with seven tamoxifen or 4-hydroxytamoxifen. Results showed that the liver weights and microsomal rates were not changed by tamoxifen or 4-hydroxytamoxifen treatment. Moreover, the uterine weights were significantly decreased and uterine peroxidase activity was marginally decreased in tamoxifen or 4-hydroxytamoxifen treated rats. In addition, hepatic DNA adduct levels in rats treated with 4-hydroxytamoxifen did not differ from control rats. Similaryly, the adduct levels in uterus DNA from rats treated with tamoxifen or 4-hydroxytamoxifen were not different from those in control rats [2].

Clinical trial: Previous clinical study showed that the antiproliferative effect of 4-hydroxytamoxifen gel to breast skin was similar to that of oral tamoxifen, but the effects on endocrine and coagulation parameters decreased [3].

参考文献:
[1] 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.
[2] Beland FA,McDaniel LP,Marques MM.  Comparison of the DNA adducts formed by tamoxifen and 4-hydroxytamoxifen in vivo. Carcinogenesis.1999 Mar;20(3):471-7.
[3] Lee O et al.  A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clin Cancer Res.2014 Jul 15;20(14):3672-82.