WIN 18446

ALDH1a2 inhibitor CAS# 1477-57-2

WIN 18446

Catalog No. BCC6273----Order now to get a substantial discount!

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Quality Control of WIN 18446

Number of papers citing our products

Chemical structure

WIN 18446

3D structure

Chemical Properties of WIN 18446

Cas No. 1477-57-2 SDF Download SDF
PubChem ID 15134 Appearance Powder
Formula C12H20Cl4N2O2 M.Wt 366.11
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in DMSO and to 20 mM in ethanol
Chemical Name 2,2-dichloro-N-[8-[(2,2-dichloroacetyl)amino]octyl]acetamide
SMILES C(CCCCNC(=O)C(Cl)Cl)CCCNC(=O)C(Cl)Cl
Standard InChIKey FAOMZVDZARKPFJ-UHFFFAOYSA-N
Standard InChI 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)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of WIN 18446

DescriptionInhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2) (IC50 = 0.3 μM). Inhibits the biosynthesis of retinoic acid from retinol in neonatal and adult murine testis.

WIN 18446 Dilution Calculator

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WIN 18446 Molarity Calculator

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Preparing Stock Solutions of WIN 18446

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.7314 mL 13.6571 mL 27.3142 mL 54.6284 mL 68.2855 mL
5 mM 0.5463 mL 2.7314 mL 5.4628 mL 10.9257 mL 13.6571 mL
10 mM 0.2731 mL 1.3657 mL 2.7314 mL 5.4628 mL 6.8285 mL
50 mM 0.0546 mL 0.2731 mL 0.5463 mL 1.0926 mL 1.3657 mL
100 mM 0.0273 mL 0.1366 mL 0.2731 mL 0.5463 mL 0.6829 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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References on WIN 18446

Testicular toxicity of WIN 18446 in the laboratory mouse.[Pubmed:8563190]

Reprod Toxicol. 1995 Sep-Oct;9(5):475-81.

The effect of oral administration of N,N'=bis (dichloroacetyl)-1, 8-octamethylenediamine (WIN 18446) (200 mg/kg body weight/day, up to 30 days) on the testis of the Parkes (P) strain laboratory mouse was studied. The drug caused reduction in testicular weight and severe atrophic changes in the seminiferous tubules. A duration-dependent effect of the drug was observed on the germ cells. The drug had its initial impact on spermatids followed by spermatocytes, ultimately culminating in the Sertoli cell-spermatogonia syndrome. The drug-induced changes included exfoliation of germ cells, formation of multinucleated giant cells, and vacuolization of cytoplasm and displacement (towards the lumina of the tubules) of Sertoli cell nuclei. Even 75 days after drug withdrawal, testicular weight remained depressed and in 15 to 20% of the tubules there was incomplete recovery of spermatogenesis. Our data indicate that WIN 18446 induces sustained impairment of spermatogenesis by a direct action on spermatogonia or indirectly by affecting the integrity of the Sertoli cells. The Leydig cells remained unaffected in WIN 18446-treated mice.

Short-term effects of N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446) on the testes, selected sperm parameters and fertility of male CBA mice.[Pubmed:14599310]

Lab Anim. 2003 Oct;37(4):363-73.

N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446), the most potent of the diamines and one of the least amoebicidal agents, was shown to exert a specific effect on the testes of CBA mice, while the Leydig cells were unaffected. Spermatogenesis was severely affected after a 42-day treatment period with 125 mg WIN 18446/kg body weight. Large multinucleated cells, vacuolization and the absence of sperm within the testes were evident in most seminiferous tubules. After 15 days of withdrawal of WIN 18446, there was a slight recovery of spermatogenesis and after withdrawal of 42 days a marked recovery of spermatogenesis. The normality or abnormality of this spermatogenic cycle could be evaluated using the semi-quantitative Stages program. There was a significant decrease in the diameters of seminiferous tubules of WIN 18446 treated mice, however an almost complete recovery was evident after 42 days of withdrawal of WIN 18446. A significant decrease in sperm concentration and sperm morphology was observed for the WIN 18446 treated mice. Various sperm motion parameters were assessed for the different treatment groups and compared to the control group. The female and male fertility indices were assessed and compared for the different treatment groups. Complete recovery of the above-mentioned parameters was evident after 42 days of withdrawal from WIN 18446, and this confirms its potential as a possible contraceptive for animal populations.

Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.[Pubmed:24711451]

J Biol Chem. 2014 May 23;289(21):15104-17.

Knowledge of the regulation of testicular retinoic acid synthesis is crucial for understanding its role in spermatogenesis. Bisdichloroacetyldiamines strongly inhibit spermatogenesis. We reported previously that one of these compounds, WIN 18,446, potently inhibited spermatogenesis in rabbits by inhibiting retinoic acid synthesis. To understand how WIN 18,446 inhibits retinoic acid synthesis, we characterized its effects on human retinal dehydrogenase ALDH1A2 in vitro as well as its effects on retinoid metabolism in vivo using mice. WIN 18,446 strongly and irreversibly inhibited ALDH1A2 in vitro. In vivo, WIN 18,446 treatment completely abolished spermatogenesis after 4 weeks of treatment and modestly reduced adiposity in mice fed a chow diet. Effects of WIN 18,446 on retinoid concentrations were tissue-dependent. Although lung and liver retinyl ester concentrations were lower in WIN 18,446-treated animals, adipose retinyl ester levels were increased following the treatment. Interestingly, animals treated with WIN 18,446 had significantly higher circulating retinol concentrations compared with control mice. The effect on spermatogenesis by WIN 18,446 was not prevented by simultaneous treatment with retinoic acid, whereas effects on other tissues were partially or completely reversed. Cessation of WIN 18,446 treatment for 4 weeks reversed most retinoid-related phenotypes except for inhibition of spermatogenesis. Our data suggest that WIN 18,446 may be a useful model of systemic acquired retinoic acid deficiency. Given the effects observed in our study, inhibition of retinoic acid biosynthesis may have relevance for the treatment of obesity and in the development of novel male contraceptives.

Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis.[Pubmed:20705791]

J Androl. 2011 Jan-Feb;32(1):111-9.

The bisdichloroacetyldiamine WIN 18,446 reversibly inhibits spermatogenesis in many species, including humans; however, the mechanism by which WIN 18,446 functions is unknown. As retinoic acid is essential for spermatogenesis, we hypothesized that WIN 18,446 might inhibit retinoic acid biosynthesis from retinol (vitamin A) within the testes by inhibiting the enzyme aldehyde dehydrogenase 1a2 (ALDH1a2). We studied the effect of WIN 18,446 on ALDH1a2 enzyme activity in vitro, and on spermatogenesis and fertility in vivo, in mature male rabbits for 16 weeks. WIN 18,446 markedly inhibited ALDH1a2 enzyme activity in vitro with an IC(50) of 0.3 muM. In vivo, the oral administration of 200 mg/kg WIN 18,446 to male rabbits for 16 weeks significantly reduced intratesticular concentrations of retinoic acid, severely impaired spermatogenesis, and caused infertility. Reduced concentrations of intratesticular retinoic acid were apparent after only 4 weeks of treatment and preceded the decrease in sperm counts and the loss of mature germ cells in tissue samples. Sperm counts and fertility recovered after treatment was discontinued. These findings demonstrate that bisdichloroacetyldiamines such as WIN 18,446 reversibly suppress spermatogenesis via inhibition of testicular retinoic acid biosynthesis by ALDH1a2. These findings suggest that ALDH1a2 is a promising target for the development of a reversible, nonhormonal male contraceptive.

Suppression of Stra8 expression in the mouse gonad by WIN 18,446.[Pubmed:21209416]

Biol Reprod. 2011 May;84(5):957-65.

Bis-(dichloroacetyl)-diamines (BDADs) are compounds that inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully investigated. It has been proposed that BDADs may function via inhibition of testicular retinoic acid (RA) biosynthesis. We employed an organ culture technique and the expression of a marker for RA activity, Stra8 (stimulated by retinoic acid gene 8), to investigate if the BDAD WIN 18,446 inhibited the biosynthesis of RA from retinol (ROL) in neonatal and adult murine testis and in the embryonic murine gonad. After culturing either whole testes or germ cells isolated from mice at 2 days postpartum (dpp) with WIN 18,446 or with WIN 18,446 plus ROL, Stra8 expression was suppressed, demonstrating that WIN 18,446 inhibited the conversion of ROL to RA in both systems. We also utilized a transgenic mouse containing an RA-responsive LacZ reporter gene to demonstrate limited RA induction of LacZ expression in 2-dpp testes cultured with WIN 18,446 plus ROL. The expression of Stra8 was downregulated in adult mouse testis tubules cultured with WIN 18,446 when compared to tubules cultured with the vehicle control. WIN 18,446 also inhibited the conversion of ROL to RA in embryonic ovaries and testes cultured for 48 h. These murine results provide critical insights regarding how the BDADs can inhibit spermatogenesis by blocking the ability of vitamin A to drive germ cell development. In addition, these techniques will be useful for screening novel inhibitors of RA biosynthesis as potential male contraceptives.

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