4-Hydroxytamoxifen is an Orally Active Selective Estrogen Receptor Modulator (SERM)

Selective estrogen receptor modulator (SERM) is a kind of drugs that act on estrogen receptor (ER). Specifically, they act as estrogen receptor agonists or antagonists in a tissue-specific manner. Besides, SERM is used in various estrogen-related diseases. SERM is also used in combination with conjugated estrogen for estrogen deficiency symptoms and menopausal-related vasomotor symptoms.

Moreover, estrogen receptors have two subunits(α And β Chain) and SERM interacts with any of them. From this interaction, SERM has a certain degree of target specificity and tissue specificity. Furthermore, they show that different ER ligands induce different structural changes in the receptor and affect its ability to interact with other proteins. These proteins are essential for regulating target gene transcription. Meanwhile, the relative expression of CO activators and inhibitors affect the biological characteristics of SERM. Nonetheless, the properties of endoplasmic reticulum and its target gene promoters also affect it. Additionally, SERM selectivity reflects the diversity of ER forms and co regulators, the differences of cell types and ER target genes. Today, we will introduce a selective estrogen receptor modulator (SERM), 4-Hydroxytamoxifen.

4-Hydroxytamoxifen is an Orally Active Selective Estrogen Receptor Modulator (SERM).

First of all, 4-Hydroxytamoxifen is a selective estrogen receptor antagonist with potent anti-estrogenic activity. Importantly, 4-Hydroxytamoxifen has an IC50 of 3.3 nM for the [3H]oestradiol binding to oestrogen receptor.

In the second place, 4-Hydroxytamoxifen with 10, 100 nM inhibits the binding of [3H]oestradiol to the human 8 S estrogen receptor. Particularly, 4-Hydroxytamoxifen activates intein-linked inactive Cas9. Obviously, 4-Hydroxytamoxifen reduces off-target CRISPR-mediated gene editing. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.

Last but not the least, 4-Hydroxytamoxifen with 0.2-5 μg/day by p.o. causes a dose-related decrease in a uterine wet weight of immature rats. 4-Hydroxytamoxifen effectively attenuates methamphetamine-induced nigrostriatal dopamine depletion in both sexes of intact and gonadectomized C57BL/6 J mice. By the way, 4-Hydroxytamoxifen does not alter the dopamine content levels in the striatum.

All in all, 4-Hydroxytamoxifen is an orally active, selective estrogen receptor modulator (SERM) with potent anti-estrogenic activity.


Kuo YM, et al. J Neurochem. 2003 Dec;87(6):1436-43.