FERTILYSIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H20Cl4N2O2
Molecular Weight	366.111
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC(Cl)C(=O)NCCCCCCCCNC(=O)C(Cl)Cl

InChI

InChIKey=FAOMZVDZARKPFJ-UHFFFAOYSA-N

InChI=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)

HIDE SMILES / InChI

Molecular Formula	C12H20Cl4N2O2
Molecular Weight	366.111
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22995542
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25502770 | https://www.ncbi.nlm.nih.gov/pubmed/8563190 | https://www.ncbi.nlm.nih.gov/pubmed/20705791

Oral administration of fertilysin (WIN 18446; N,N’-bis(dichloroacetyl)-1,8-octamethylenediamine) led to a complete arrest of spermatogenesis. Fertilysin was found to be a safe, effective, and reversible oral contraceptive in male animals (rodents, wolves, cats, and shrews). The utility of fertilysin as a contraceptive in man is hampered by the fact that men taking fertilysin experience a “disulfiram reaction” when they drink alcohol. Fertilysin suppresses spermatogenesis by inhibiting testicular retinoic acid biosynthesis. In vitro, it inhibits the function of aldehyde dehydrogenase 1A (ALDH1A) enzymes, which function in testicular retinoic acid biosynthesis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Retinal dehydrogenase 2 5 Target ID: CHEMBL3112384 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20705791 \| https://www.ncbi.nlm.nih.gov/pubmed/24711451 \| https://www.ncbi.nlm.nih.gov/pubmed/25502770	Inhibitor 8297	1026.0 nM [Ki]
Aldehyde dehydrogenase 1A1 5 Target ID: CHEMBL3577 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25502770	Inhibitor 8297	102.0 nM [IC50]
Aldehyde dehydrogenase 1A3 1 Target ID: CHEMBL3579 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25502770	Inhibitor 8297	187.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Male fertility 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13695940 https://www.ncbi.nlm.nih.gov/pubmed/20705791 https://www.ncbi.nlm.nih.gov/pubmed/8563190 http://www.newmalecontraception.org/wp-content/uploads/2014/03/History-of-Male-Contraception.pdf	Preventing		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The biologic actions of a new series of bis(dichloroacetyl) diamines.	1960 Nov	13695940
Efficacy, safety and reversibility of bisdiamine as a male contraceptive in cats.	2004 Jul	15159103
Teratogenic effects of bis-diamine on the developing cardiac conduction system.	2005 Aug	15965974
Morphological differences in cardiovascular anomalies induced by bis-diamine between Sprague-Dawley and Wistar rats.	2005 Jun	15904432
Reaction coordinate of a functional model of tyrosinase: spectroscopic and computational characterization.	2009 May 13	19368383
Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis.	2011 Jan-Feb	20705791
A screen for disruptors of the retinol (vitamin A) signaling pathway.	2013 Jun	23696197
Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.	2014 May 23	24711451

Patents

Sample Use Guides

In Vivo Use Guide

Oral fertilysin (WIN 18446) (200 mg/kg body weight/day, up to 30 days) induces sustained impairment of spermatogenesis by a direct action on spermatogonia or indirectly by affecting the integrity of the Sertoli cells. Oral administration of 200 mg/kg fertilysin to male rabbits for 16 weeks significantly reduced intratesticular concentrations of retinoic acid, severely impaired spermatogenesis, and caused infertility.

Route of Administration: Oral

In Vitro Use Guide

1 uM fertilysin (WIN 18446) inhibits Stra8 expression in mouse gonocyte cultures

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:39:50 UTC 2023` Edited by `admin` on `Fri Dec 15 16:39:50 UTC 2023`
Record UNII	3F56RA64JN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FERTILYSIN

Common Name

English

N,N'-1,8-OCTANEDIYLBIS(2,2-DICHLOROACETAMIDE)

Systematic Name

English

N,N'-OCTAMETHYLENEBIS(2,2-DICHLOROACETAMIDE)

Systematic Name

English

WIN-18446

Code

English

N,N'-OCTAMETHYLENE BIS(2,2-DICHLORO ACETAMIDE)

Common Name

English

N,N'-BIS(DICHLOROACETYL)-1,8-OCTAMETHYLENEDIAMINE

Common Name

English

NSC-59354

Code

English

FERTILYSIN [MI]

Common Name

English

Code System Code Type Description

MERCK INDEX

m5357