{{Short description|Chemical compound}} {{Orphan|date=August 2023}}
{{Infobox drug | drug_name = | INN = | type = <!-- empty --> | image = Fertilysin.svg | image_class = skin-invert-image | alt = | caption = <!-- Clinical data --> | pronounce = | tradename = | synonyms = WIN 18446 | Drugs.com = | MedlinePlus = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = | ATCvet = | ATC_prefix = <!-- 'none' if uncategorised --> | ATC_suffix = <!-- Legal status --> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US_comment = | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above --> <!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action= | excretion = <!-- Identifiers --> | CAS_number = 1477-57-2 | PubChem = 15134 | UNII = 3F56RA64JN | ChEBI = 90441 | ChEMBL = 3276621 | ChemSpiderID = 14405 | DrugBank = <!-- Chemical and physical data --> | IUPAC_name = 2,2-Dichloro-''N''-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide | C = 12 | H = 20 | Cl = 4 | N = 2 | O = 2 | StdInChI=1S/C12H20Cl4N2O2/c13-9(14)11(19)17-7-5-3-1-2-4-6-8-18-12(20)10(15)16/h9-10H,1-8H2,(H,17,19)(H,18,20) | StdInChIKey = FAOMZVDZARKPFJ-UHFFFAOYSA-N | smiles = ClC(C(NCCCCCCCCNC(C(Cl)Cl)=O)=O)Cl }}
'''Fertilysin''' ('''WIN 18446''') is an experimental drug that was studied as a male contraceptive, but was never marketed. It interferes with testicular production of retinoic acid,<ref>{{cite journal | vauthors = Paik J, Haenisch M, Muller CH, Goldstein AS, Arnold S, Isoherranen N, Brabb T, Treuting PM, Amory JK | display-authors = 6 | title = Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice | journal = The Journal of Biological Chemistry | volume = 289 | issue = 21 | pages = 15104–15117 | date = May 2014 | pmid = 24711451 | pmc = 4031560 | doi = 10.1074/jbc.M113.540211 | doi-access = free }}</ref> which is necessary for spermatogenesis. In studies in male animals including rodents, wolves, cats, and shrews, fertilysin was found to be a safe, effective, and reversible oral contraceptive.<ref>{{cite journal | vauthors = Heller CG, Moore DJ, Paulsen CA | title = Suppression of spermatogenesis and chronic toxicity in men by a new series of bis(dichloroacetyl) diamines | journal = Toxicology and Applied Pharmacology | volume = 3 | pages = 1–11 | date = January 1961 | issue = 1 | pmid = 13713106 | doi = 10.1016/0041-008x(61)90002-3 | bibcode = 1961ToxAP...3....1H }}</ref><ref name=Inxight>{{cite web | url = https://drugs.ncats.io/substance/3F56RA64JN | title = Fertilysin | work = Inxight Drugs | publisher = National Center for Advancing Translational Sciences (NCAT): U.S. National Institutes of Health }}</ref> However, the side effects observed in human clinical trials preclude its use in men.<ref name=sciencehistory>{{cite web | vauthors = Kean S | title = Why Don't We Have a Male Birth Control Pill Yet? | date = April 20, 2021 | publisher = Science History Institute | url = https://sciencehistory.org/stories/disappearing-pod/why-dont-we-have-a-male-birth-control-pill-yet/}}</ref>
Fertilysin was originally studied in the 1950s for its potential amebicidal effects.<ref name=sciencehistory/><ref>{{cite journal | doi = 10.4269/ajtmh.1961.10.503 | title = N,N′-bis(Dichloroacetyl)Diamines as Amebicidal Agents | date = 1961 | vauthors = Berberian DA, Slighter RG, Dennis EW | journal = The American Journal of Tropical Medicine and Hygiene | volume = 10 | issue = 4 | pages = 503–509 }}</ref><ref>{{cite journal | vauthors = Coulston F, Beyler AL, Drobeck HP | title = The biologic actions of a new series of bis(dichloroacetyl) diamines | journal = Toxicology and Applied Pharmacology | volume = 2 | issue = 6 | pages = 715–731 | date = November 1960 | pmid = 13695940 | doi = 10.1016/0041-008X(60)90088-0 | bibcode = 1960ToxAP...2..715C }}</ref> When the anti-spermatogenesis effects were observed in animal studies, the focus of the research turned towards its potential use as a contraceptive. Fertilysin is an inhibitor of aldehyde dehydrogenase 1a2, a member of the aldehyde dehydrogenase family of enzymes. Inhibition of this enzyme blocks the production of retinoic acid which prevents the production of sperm. Because aldehyde dehydrogenases are also involved in the metabolism of ethanol, fertilysin has side effects similar to the action of disulfiram (Antabuse).<ref name=Inxight/> Fertilysin may also have teratogenic effects.<ref>{{cite journal | vauthors = Binder M | title = The teratogenic effects of a bis(dichloroacetyl)diamine on hamster embryos. Aortic arch anomalies and the pathogenesis of the DiGeorge syndrome | journal = The American Journal of Pathology | volume = 118 | issue = 2 | pages = 179–193 | date = February 1985 | pmid = 3970137 | pmc = 1887872 }}</ref>
== References == {{reflist}}
Category:Abandoned drugs Category:Amides Category:Dichloromethyl compounds Category:Contraception for males