human magl

URB754 is a potent and noncompetitive inhibitor of monoacylglycerol lipase (MAGL), exhibiting an IC50 value of 200 nM for the recombinant rat brain enzyme. However, it does not inhibit human recombinant, rat brain, or mouse brain MAGL at concentrations up to 100 μM. There is evidence that the MAGL inhibitory activity of URB754 may be attributed to the impurity bis(methylthio)mercurane (IC50 = 11.9 nM for rat recombinant MAGL) that is found in commercial preparations. URB754 inhibits rat brain fatty acyl amide hydrolase (FAAH) with an IC50 value of 32 μM and binds weakly to the rat central cannabinoid (CB1) receptor with an IC50 value of 3.8 μM. It does not inhibit COX-1 or COX-2 at concentrations up to 100 μM. Inhibition of MAGL hydrolysis of 2-arachidonoyl glycerol (2-AG) is associated with enhanced stress-induced analgesia and may represent a novel drug target in pain and stress management.

MAGLi 432 is a potent, highly selective, non-covalent, reversible (MAGL) inhibitor that binds with high affinity to the MAGL active site, with IC50 values of 4.2 nM (human enzyme) and 3.1 nM (mouse enzyme), MAGLi 432 can be used to study neurological disorders such as chronic inflammation, multiple sclerosis, blood-brain barrier dysfunction, Alzheimer's disease and Parkinson's disease.

MAGL-IN-8 (compound 13) is a reversible inhibitor of monoacylglycerol lipase (MAGL) with an IC50 value of 2.5 ± 0.4 nM for human MAGL (hMAGL) [1].

AKU-005 is a dual inhibitor of FAAH and MAGL, exhibiting IC50 values of 63 nM and 389 nM against rat and human FAAH, respectively. This compound has potential for researching trigeminal nociceptive hypersensitivity.