Merck, 475741-10MG, MAGL Inhibitor III, JZL184

General description
A cell-permeable, blood-brain-barrier-permeant, and orally available carbamate compound that selectively inhibit MAGL (monoacylglycerol lipase) activity over FAAH (fatty acid amide hydrolase) and 35 other murine brain serine hydrolases, both in vitro (IC₅₀ = 6 - 8 nM against 2-AG hydrolysis by MAGL vs. 4 µM against anandamide/AEA hydrolysis by FAAH) and in mice in vivo (5-fold 2-AG enhancement and 75% MAGL activity inhibition in brain membrane from mice 4 hr after a single JZL184 dosage at 4 mg/kg via i.p.) in an irreversible, time- and dose-dependent manner. A great complement to the FAAH inhibitor URB597 (Cat. No. 341249 ) in differentiating the roles of CB1 and CB2 (type I and II cannabinoid receptors) in eCB- (endocannabinoid) mediated cellular signaling and in vivo physiological effects. Reported to be equally effective against human and murine MAGL, but inhibit rat MAGL with a ~10-fold lower potency.
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Nomura, D.K., et al. 2010. Cell140, 49.
Long, J.Z., et al. Nature Chem. Biol.16, 744.
Long, J.Z., et al. 2009. Nature Chem. Biol.5, 37.
Pan, B., et al. 2009. J. Pharmacol. Exp. Ther.331, 591.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)