Uses
Endocannabinoids such as 2-arachidonoyl glycerol (2-AG; ) and arachidonoyl ethanolamide (AEA; ) are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid (CB) receptors. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mediate the hydrolysis of AEA and 2-AG, respectively. Monoacylglycerol Lipase Inhibitor 21 selectively binds to MAGL (Ki = 0.4 μM) and reversibly blocks the enzyme’s activity in mouse brain with an IC50 value of 0.18 μM. Comparatively, Monoacylglycerol Lipase Inhibitor 21 is reported to inhibit FAAH activity in mouse brain with an IC50 value of 59 μM. This compound does not bind CB1 or CB2 receptors and does not inhibit the related serine hydrolases ABHD6 and ABHD12 (Kis > 10 μM). In a mouse model of multiple sclerosis, 5 mg/kg of Monoacylglycerol Lipase Inhibitor 21 has been used to ameliorate progression of the disease without producing detrimental CB1-mediated effects.[Cayman Chemical]
Uses
Monoacylglycerol Lipase Inhibitor 21 is an enzyme governing the inactivation of endocannabinoid 2-arachidonoglycerol (2-AG)MAGL inhibitors display analgesic and tissue-protecting effects.
Biological Activity
ki: 0.4 μm for maglmonoacylglycerol lipase inhibitor 21 is an inhibitor of monoacylglycerol lipase (magl) and faah.endocannabinoids such as 2-arachidonoyl glycerol (2-ag) and arachidonoyl ethanolamide (aea) are biologically active lipids involved in various synaptic processes including activation of cannabinoid receptors. fatty acid amide hydrolase (faah) and monoacylglycerol lipase (magl) mediate the hydrolysis of aea and 2-ag, respectively.
in vitro
a previous study confirmed that monoacylglycerol lipase inhibitor 21 could inhibit magl in a reversible manner. moreover, the kinetic studies indicated that monoacylglycerol lipase inhibitor 21 acted as a noncompetitive inhibitor. in addition, monoacylglycerol lipase inhibitor 21 did not bind cb1 or cb2 receptors. furthermore, the selectivity of monoacylglycerol lipase inhibitor 21 was studied in a broad panel that includes a variety of receptors and enzymes, and the results showed that monoacylglycerol lipase inhibitor 21 did not inhibit significantly any of the analyzed targets [1].
in vivo
multiple sclerosis (ms) mouse model was used to evaluated the in-vivo efficacy of monoacylglycerol lipase inhibitor 21. treatment started at day 6 post-immunization and consisted of daily injections of monoacylglycerol lipase inhibitor 21 (5 mg/kg, i.p.) for the following 21 days. results showed that the administration of monoacylglycerol lipase inhibitor 21 could clearly ameliorate the progression of the disease, as assessed by the significantly lower clinical score in the ms model. this improvement correlated with an increase of the 2-ag levels in the spinal cord of treated animalsand with evident changes at the histological level, as monoacylglycerol lipase inhibitor 21 was able to significantly decrease leukocyte infiltration and microglial response, prevent axonal damage, as well as partially restore myelin morphology in eae mice [1].
References
[1] hernández-torres, g. ,cipriano, m.,hedén, e., et al. a reversible and selective inhibitor of monoacylglycerol lipase ameliorates multiple sclerosis. angewandte chemistry international edition english 53(50), 13765-13770 (2014).
