| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
The primary target of JW642 is monoacylglycerol lipase (MAGL), the principal enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. MAGL is a serine hydrolase that terminates 2-AG signaling by converting it to arachidonic acid and glycerol. By inhibiting MAGL, JW642 increases brain levels of 2-AG, thereby enhancing endocannabinoid signaling. The compound shows >1000-fold selectivity for MAGL over FAAH (IC₅₀ = 20.6 μM), making it a highly specific tool for studying MAGL function.
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| ln Vitro |
In vitro, JW642 is a potent inhibitor of MAGL with IC₅₀ values of 7.6, 14, and 3.7 nM for inhibition of MAGL in mouse, rat, and human brain membranes, respectively. It displays >1000-fold selectivity for MAGL over FAAH (IC₅₀ = 20.6 μM). The compound's high potency and selectivity make it a valuable tool for studying MAGL function and endocannabinoid signaling. However, it does not effectively inhibit FAAH activity (IC₅₀ = 31 μM).
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| ln Vivo |
In vivo, JW642 is used in preclinical research to study the role of 2-AG in the central nervous system, including pain, anxiety, and neurodegenerative disorders. By inhibiting MAGL, the compound increases brain levels of 2-AG, thereby modulating endocannabinoid-mediated signaling pathways. JW642 serves as a valuable pharmacological tool for dissecting endocannabinoid-mediated signaling pathways and potential therapeutic strategies. However, specific in vivo efficacy data is not detailed in the available sources.
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| Enzyme Assay |
For MAGL inhibitors, standard cell-free assays involve measuring the hydrolytic activity of MAGL using a fluorogenic substrate (e.g., 7-hydroxycoumarinyl arachidonate or arachidonoyl-AMC) or radiolabeled 2-oleoylglycerol. The compound is incubated with the enzyme and substrate, and the release of fluorescent or radiolabeled product is measured to determine IC₅₀ values. Selectivity for MAGL over FAAH is assessed using FAAH enzyme assays.
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| Cell Assay |
For MAGL inhibitors, standard cellular assays involve treatment of cells (e.g., neuroblastoma cells or primary neurons) with the test compound for 1-4 hours. 2-AG levels in cell lysates are measured by LC-MS. MAGL activity is assessed by measuring the hydrolysis of a fluorogenic substrate in cell lysates. Effects on downstream signaling (e.g., cannabinoid receptor activation, ERK phosphorylation) are also measured.
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| Animal Protocol |
For in vivo evaluation of MAGL inhibitors, standard animal models include pain models (e.g., formalin test, neuropathic pain), anxiety models (e.g., elevated plus maze, open field), and neurodegenerative disease models. The compound is typically administered orally or intraperitoneally, and behavioral, biochemical, and pharmacological endpoints are assessed. JW642 is primarily used in preclinical research.
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| ADME/Pharmacokinetics |
JW642 has a molecular weight of 462.39 and formula C₂₁H₂₀F₆N₂O₃. It is soluble in DMF at 11 mg/mL, DMSO at 5 mg/mL, ethanol at 13 mg/mL, and ethanol:PBS (pH 7.2) (1:2) at 0.3 mg/mL. The compound has a purity of ≥98% and should be stored at -20°C for long-term stability. Comprehensive PK studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for JW642 is not provided in the available sources. As a research compound targeting MAGL, standard preclinical toxicology would be required for therapeutic development. The compound's high selectivity for MAGL over FAAH suggests a favorable specificity profile. However, potential effects on other serine hydrolases would need to be assessed. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
JW642 is a potent and selective MAGL inhibitor with IC₅₀ values of 7.6, 14, and 3.7 nM for inhibition of MAGL in mouse, rat, and human brain membranes, respectively. It displays >1000-fold selectivity for MAGL over FAAH (IC₅₀ = 20.6 μM). The compound is an analog of JZL 195 and is primarily used in preclinical research to study the role of 2-AG in the CNS. No regulatory approval has been identified.
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| Molecular Formula |
C21H20F6N2O3
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|---|---|
| Molecular Weight |
462.39
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| Exact Mass |
462.137
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| CAS # |
1416133-89-5
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| PubChem CID |
71656520
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
432.9±45.0 °C at 760 mmHg
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| Flash Point |
215.6±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.511
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| LogP |
6.43
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
587
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AVSCNEOUWSVZEY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20F6N2O3/c22-20(23,24)18(21(25,26)27)32-19(30)29-11-9-28(10-12-29)14-15-5-4-8-17(13-15)31-16-6-2-1-3-7-16/h1-8,13,18H,9-12,14H2
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| Chemical Name |
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[(3-phenoxyphenyl)methyl]piperazine-1-carboxylate
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| Synonyms |
JW 642; JW-642; JW642
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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 (~216.27 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1627 mL | 10.8134 mL | 21.6268 mL | |
| 5 mM | 0.4325 mL | 2.1627 mL | 4.3254 mL | |
| 10 mM | 0.2163 mL | 1.0813 mL | 2.1627 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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