|Other names||Enclomiphene; (E)-Clomifene; RMI-16289; Enclomid; Enclomifene citrate; Enclomiphene citrate|
|Drug class||Selective estrogen receptor modulator; Progonadotropin|
|Chemical and physical data|
|Molar mass||405.97 g·mol−1|
|3D model (JSmol)|
Enclomifene (INN) (former tentative brand names Androxal and EnCyzix), or enclomiphene (USAN), is a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group which was under development for the treatment of male hypogonadism and type 2 diabetes. By December 2016, it was in preregistration and was under review by the Food and Drug Administration in the United States and the European Medicines Agency in the European Union. In January 2018, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended refusal of marketing authorization for enclomifene for the treatment of secondary hypogonadism. In April 2021, development of enclomifene was discontinued for all indications.
Enclomifene acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin secretion and hence gonadal production of testosterone. It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene. Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer. Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic. In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men. As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.