Win 18446 is an orally bioactive inhibitor of the testis-specific enzyme ALDH1a2 with IC50 of 0.3 μM. Win 18446 reversibly inhibits spermatogenesis in multiple species and inhibits the synthesis of retinoic acid from retinol in the testes.

Physicochemical Properties

Molecular Formula	C12H20CL4N2O2
Molecular Weight	366.11
Exact Mass	364.027
CAS #	1477-57-2
PubChem CID	15134
Appearance	Solid powder
Density	1.3±0.1 g/cm3
Boiling Point	530.2±50.0 °C at 760 mmHg
Melting Point	118-120ºC
Flash Point	274.5±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.503
LogP	1.96
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	11
Heavy Atom Count	20
Complexity	261
Defined Atom Stereocenter Count	0
InChi Key	FAOMZVDZARKPFJ-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	2,2-dichloro-N-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	ALDH1
ln Vitro	Stra8 expression in entire testis cultures containing germ cells and somatic cells is inhibited by WIN 18446 (1 μM, 24 hours) [2].
ln Vivo	Win 18446 (200 mg/kg, taken orally for 4, 8, and 16 weeks) causes severe impairments to spermatogenesis, a major decrease in intratesticular retinoic acid concentration, and ultimately sterility[1].
Cell Assay	RT-PCR[2] Cell Types: Testes were collected from 2-dpp mice. Tested Concentrations: 1 μM. Incubation Duration: 24 h. Experimental Results: Results in a VAD-like phenotype in the testis. Alone or in combination with ROL Dramatically diminished Stra8 expression.
Animal Protocol	Animal/Disease Models: Six-month-old male New Zealand white rabbits[1]. Doses: 200 mg/kg. Route of Administration: Orally for 4, 8, and 16 weeks. Experimental Results: Resulted in marked suppression of testicular weight over time. Dramatically suppressed spermatogenesis. Dramatically reduces intratesticular concentrations of retinoic acid and Stra8 expression and very severely suppresses spermatogenesis and fertility.
References	[1]. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl. Jan-Feb 2011;32(1):111-9. [2]. Suppression of Stra8 expression in the mouse gonad by WIN 18,446. Biol Reprod. 2011 May;84(5):957-65.
Additional Infomation	WIN 18446 is a carboxamide that is 1,8-diaminooctane in which a hydrogen attached to each of the amino groups has been replaced by a dichloroacetyl group. Inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2). Inhibits the biosynthesis of retinoic acid from retinol in neonatal and adult murine testis. It down-regulates sex related genes in zebrafish. It has a role as an EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor. It is an organochlorine compound and a secondary carboxamide. It is functionally related to a dichloroacetic acid and a 1,8-diaminooctane.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (273.14 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7314 mL	13.6571 mL	27.3142 mL
	5 mM	0.5463 mL	2.7314 mL	5.4628 mL
	10 mM	0.2731 mL	1.3657 mL	2.7314 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.