Enclomifene

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.[1][2][3][4] 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.[3] 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.[5] In April 2021, development of enclomifene was discontinued for all indications.[3]

Enclomifene
Clinical data
Trade namesAndroxal
Other namesEnclomiphene; (E)-Clomifene; RMI-16289; Enclomid; Enclomifene citrate; Enclomiphene citrate
Routes of
administration		By mouth
Drug classSelective estrogen receptor modulator; Progonadotropin
Identifiers
  • 2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC26H28ClNO
Molar mass405.97 g·mol−1
3D model (JSmol)
  • CCN(CC)CCOC1=CC=C(C=C1)/C(=C(\C2=CC=CC=C2)/Cl)/C3=CC=CC=C3
  • InChI=1S/C26H28ClNO/c1-3-28(4-2)19-20-29-24-17-15-22(16-18-24)25(21-11-7-5-8-12-21)26(27)23-13-9-6-10-14-23/h5-18H,3-4,19-20H2,1-2H3/b26-25+
  • Key:GKIRPKYJQBWNGO-OCEACIFDSA-N

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.[4] It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene.[4] Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer.[1][2] Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic.[4] In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men.[4] As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.[4]

References
  1. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 298–. ISBN 978-1-4757-2085-3.
  2. I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 79–. ISBN 978-0-7514-0499-9.
  3. "Enclomifene - Repros Therapeutics - AdisInsight".
  4. Hill S, Arutchelvam V, Quinton R (2009). "Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men". IDrugs. 12 (2): 109–19. PMID 19204885.
  5. http://www.ema.europa.eu/en/medicines/human/EPAR/encyzix



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