| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
ALDH1
The primary target of Win 18446 is ALDH1A2 (also known as retinaldehyde dehydrogenase 2), a testes-specific enzyme that catalyzes the oxidation of retinaldehyde to retinoic acid. Win 18446 is a pan-ALDH1a2 inhibitor with an IC50 of 0.3 μM in vitro. By inhibiting ALDH1A2, the compound blocks retinoic acid biosynthesis from retinol within the testes, which is essential for spermatogenesis. The inhibition is reversible, and spermatogenesis can resume upon withdrawal of the compound. |
|---|---|
| ln Vitro |
Stra8 expression in entire testis cultures containing germ cells and somatic cells is inhibited by WIN 18446 (1 μM, 24 hours) [2].
In vitro, Win 18446 inhibits ALDH1a2 enzymatic activity with an IC50 of 0.3 μM. The compound is a pan-ALDH1a2 inhibitor and shows activity against the testes-specific enzyme. In cell-based studies, Win 18446 has been shown to downregulate sex-related genes in zebrafish. The compound's ability to inhibit ALDH1A2 makes it a valuable tool for studying the role of retinoic acid in spermatogenesis and other physiological processes. |
| 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].
In vivo, Win 18446 is orally active and reversibly inhibits spermatogenesis in many species. The compound blocks retinoic acid biosynthesis from retinol within the testes, leading to the cessation of sperm production. The inhibition is reversible, and spermatogenesis resumes upon withdrawal of the compound. Win 18446 is being investigated for its potential applications in male contraception and retinoid pathway modulation in cancer treatment. |
| Enzyme Assay |
The in vitro enzyme assay for Win 18446 involves measuring the inhibition of ALDH1a2 enzymatic activity using recombinant ALDH1a2 enzyme. The assay is performed in a suitable buffer system containing the substrate retinaldehyde and the cofactor NAD+. Test compounds are incubated with the enzyme at various concentrations, and the formation of retinoic acid is measured using HPLC or spectrophotometric methods. IC50 values are calculated by fitting dose-response curves to the inhibition data.
|
| 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. Cellular assays for Win 18446 typically use testicular cell lines or cells treated with retinoic acid signaling reporters. Cells are treated with the test compound at various concentrations, and the inhibition of ALDH1a2 activity is measured by assessing the production of retinoic acid or by using reporter gene assays that detect retinoic acid signaling. The compound's effects on cell proliferation, differentiation, and gene expression may also be assessed. |
| 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. In vivo animal studies for Win 18446 typically involve oral administration of the compound to male rodent models. Following treatment, testicular tissue and blood samples are collected to assess spermatogenesis, retinoic acid levels, and reproductive hormone levels. The compound's ability to inhibit spermatogenesis and its reversibility are evaluated to determine its potential as a male contraceptive agent. |
| ADME/Pharmacokinetics |
Win 18446 is orally active and its pharmacokinetic properties include absorption from the gastrointestinal tract, distribution to tissues including the testes, metabolism, and excretion. The compound has a molecular weight of 366.11 and is soluble in DMSO at 20 mg/mL. For research purposes, the compound is typically stored under appropriate conditions and handled with standard safety precautions.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for Win 18446 in the available literature. As a research chemical, the compound is intended for laboratory use only and should be handled with standard safety precautions. Toxicity studies would be required if the compound were to be developed further for therapeutic applications. The compound is supplied with a purity of ≥97%.
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| References | |
| Additional Infomation |
WIN 18446 is a carboxamide with the structure 1,8-diaminooctane, in which each hydrogen atom on the amino group is replaced by a dichloroacetyl group. It is an inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2), which inhibits the conversion of retinol to retinoic acid in the testes of newborn and adult mice. It also downregulates the expression of sex-related genes in zebrafish. It is an EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor. WIN 18446 is an organochlorine compound and a secondary carboxamide. Its structure is similar to that of dichloroacetic acid and 1,8-diaminooctane.
Win 18446 is an orally active testes-specific enzyme ALDH1a2 inhibitor with an IC50 of 0.3 μM. The compound reversibly inhibits spermatogenesis in many species by blocking retinoic acid biosynthesis from retinol within the testes. Win 18446 has a molecular formula of C12H20Cl4N2O2 and a molecular weight of 366.11. It is being investigated for male contraception and retinoid pathway modulation in cancer treatment. |
| Molecular Formula |
C12H20CL4N2O2
|
|---|---|
| Molecular Weight |
366.11
|
| Exact Mass |
364.027
|
| CAS # |
1477-57-2
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| PubChem CID |
15134
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| Appearance |
Solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
530.2±50.0 °C at 760 mmHg
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| Melting Point |
118-120ºC
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| Flash Point |
274.5±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.503
|
| LogP |
1.96
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
20
|
| Complexity |
261
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(CCCCNC(=O)C(Cl)Cl)CCCNC(=O)C(Cl)Cl
|
| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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