Selective estrogen receptor modulator

Selective estrogen receptor modulator
Drug class
Tamoxifen, a nonsteroidal triphenylethylene antiestrogen and a widely used drug in the treatment of breast cancer.
Class identifiers
Synonyms	SERM
Use	Breast cancer, infertility, osteoporosis, vaginal atrophy, dyspareunia, contraception, male hypogonadism, gynecomastia, breast pain, others
ATC code	L02BB
Biological target	Estrogen receptor

Selective estrogen receptor modulators (SERMs) are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists (that is, full agonists and silent antagonists) is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

SERMs are competitive partial agonists of the ER. Different tissues have different degrees of sensitivity to and activity of endogenous estrogens, so SERMs produce estrogenic or antiestrogenic effects depending on the specific tissue in question as well as the percentage of intrinsic activity (IA) of the SERM. An example of a SERM with high IA and thus mostly estrogenic effects is chlorotrianisene, while an example of a SERM with low IA and thus mostly antiestrogenic effects is ethamoxytriphetol. SERMs like clomifene and tamoxifen are more in the middle in their IA and their balance of estrogenic and antiestrogenic actions in comparison. Raloxifene is a SERM that is more antiestrogenic than tamoxifen; both are estrogenic in bone, but raloxifene is antiestrogenic in the uterus while tamoxifen is estrogenic in this location.

The discovery of SERMs resulted from attempts to develop new contraceptives. A timeline of when SERMs came on the market is seen in figure 1. Clomifene and tamoxifen prevented conception in rats but did the opposite in humans. Clomifene successfully induced ovulation in subfertile women and on February 1, 1967, it was approved in the US for the treatment of ovulatory dysfunction in women who were trying to conceive.Toxicological issues prevented long term use of clomifene and further drug development for other potential applications such as breast cancer treatment and prevention.