Enclomifene

Enclomifene
Clinical data
Trade names	Androxal
Other names	Enclomiphene; (E)-Clomifene; RMI-16289; Enclomid; Enclomifene citrate; Enclomiphene citrate
Routes of; administration	By mouth
Drug class	Selective estrogen receptor modulator; Progonadotropin
Pharmacokinetic data
Metabolism	liver, CYP2D6 and CYP3A4
Elimination half-life	10 hours
Identifiers
	IUPAC name 2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine;
CAS Number	15690-57-0;
PubChem CID	1548953;
IUPHAR/BPS	7619;
DrugBank	DB06735;
ChemSpider	1265967;
UNII	R6D2UI4FLS;
KEGG	D10876;
ChEBI	CHEBI:3752;
ChEMBL	ChEMBL954;
CompTox Dashboard (EPA)	DTXSID201318048 ;
Chemical and physical data
Formula	C26H28ClNO
Molar mass	405.97 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN(CC)CCOC1=CC=C(C=C1)/C(=C(\C2=CC=CC=C2)/Cl)/C3=CC=CC=C3;
	InChI 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 (INNTooltip International Nonproprietary Name), or enclomiphene (USANTooltip United States Adopted Name), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group, 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.^[3] It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene.^[3] Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer.^[4]^[5] Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic.^[3] In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men.^[3] As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.^[3]

Enclomiphene (former tentative brand names Androxal and EnCyzix), was under development for the treatment of male hypogonadism and type 2 diabetes.^[4]^[5]^[6]^[3] 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.^[6] 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.^[7] In April 2021, development of enclomifene was discontinued for all indications.^[6]

^ Mikkelson TJ, Kroboth PD, Cameron WJ, Dittert LW, Chungi V, Manberg PJ (September 1986). "Single-dose pharmacokinetics of clomiphene citrate in normal volunteers". Fertility and Sterility. 46 (3): 392–396. doi:10.1016/s0015-0282(16)49574-9. PMID 3091405.
^ Ghobadi C, Gregory A, Crewe HK, Rostami-Hodjegan A, Lennard MS (2008). "CYP2D6 is primarily responsible for the metabolism of clomiphene". Drug Metabolism and Pharmacokinetics. 23 (2): 101–105. doi:10.2133/dmpk.23.101. PMID 18445989.
^ ^a ^b ^c ^d ^e ^f Hill S, Arutchelvam V, Quinton R (February 2009). "Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men". IDrugs. 12 (2): 109–119. PMID 19204885.
^ ^a ^b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 298–. ISBN 978-1-4757-2085-3.
^ ^a ^b Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 79–. ISBN 978-0-7514-0499-9.
^ ^a ^b ^c "Enclomifene - Repros Therapeutics". AdisInsight. Springer Nature Switzerland AG.
^ "EnCyzix". 17 September 2018.