JW 642

{{Infobox drug | name = JW 642 | image = | width = 250 | alt = | caption = | IUPAC_name = (3S,4S)-3-[[5-(Trifluoromethyl)pyridin-2-yl]oxy]-4-[[4-(trifluoromethyl)phenyl]methyl]oxolan-2-one | CAS_number = 1416133-89-5 | PubChem = 53302812 | ChemSpiderID = 26333212 | UNII = | KEGG = | ChEMBL = 2103875 | C=18 | H=13 | F=6 | N=1 | O=3 | smiles = C1CC(OC1C2=CC=C(C=C2)C(F)(F)F)OC3=NC=C(C=C3)C(F)(F)F }}

JW 642 is a potent and selective inhibitor of the enzyme monoacylglycerol lipase (MAGL), which plays a crucial role in the endocannabinoid system. This compound is of significant interest in the field of neuropharmacology due to its potential therapeutic applications in modulating endocannabinoid signaling.

Mechanism of Action

JW 642 functions by inhibiting the activity of MAGL, an enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), one of the primary endocannabinoids in the brain. By inhibiting MAGL, JW 642 increases the levels of 2-AG, thereby enhancing endocannabinoid signaling. This can lead to various physiological effects, including analgesia, anti-inflammatory responses, and neuroprotection.

Pharmacological Effects

Studies have shown that JW 642 exhibits a high degree of selectivity for MAGL over other serine hydrolases, such as fatty acid amide hydrolase (FAAH). This selectivity is crucial for its potential therapeutic use, as it minimizes off-target effects. The increased levels of 2-AG due to MAGL inhibition can result in:

• Analgesic effects: By modulating pain pathways, JW 642 has shown potential in reducing pain perception in various animal models.
• Anti-inflammatory effects: The compound may reduce inflammation by modulating immune cell activity and cytokine production.
• Neuroprotective effects: Enhanced endocannabinoid signaling can protect neurons from excitotoxicity and oxidative stress, suggesting potential benefits in neurodegenerative diseases.

Research and Development

JW 642 is primarily used as a research tool to study the endocannabinoid system and the role of MAGL in various physiological and pathological processes. Its ability to selectively inhibit MAGL makes it a valuable compound for investigating the therapeutic potential of endocannabinoid modulation.

Potential Therapeutic Applications

While JW 642 itself is not currently used as a therapeutic agent, its mechanism of action suggests potential applications in treating conditions such as:

• Chronic pain
• Inflammatory diseases
• Neurodegenerative disorders

Safety and Toxicology

As with many research chemicals, the safety profile of JW 642 in humans is not well-established. Studies in animal models are necessary to evaluate its toxicity, pharmacokinetics, and long-term effects.

Also see

• Endocannabinoid system
• Monoacylglycerol lipase
• 2-arachidonoylglycerol
• Fatty acid amide hydrolase