MAGL-IN-1

MAGL inhibitor compound 23 is an inhibitor of monoacylglycerol lipase (MAGL; IC₅₀ = 80 nM).¹ It is selective for MAGL over cannabinoid receptor 1 (CB₁), CB₂, fatty acid amide hydrolase (FAAH), α/β-hydrolase domain-containing protein 6 (ABHD6), and ABHD12 (IC₅₀s = >10 μM). MAGL inhibitor compound 23 inhibits the growth of HCT116, MDA-MB-231, Caov-3, OVCAR-3, and SKOV3 cells (IC₅₀s = 21, 7.9, 25, 57, and 15 μM, respectively) but not MRC5 cells (IC₅₀ = >100 μM). It increases the levels of 2-arachidonoyl glycerol (2-AG; ) in mouse brain and plasma when administered at a dose of 50 mg/kg.

1. Granchi, C., Lapillo, M., Glasmacher, S., et al. Optimization of a benzoylpiperidine class identifies a highly potent and selective reversible monoacylglycerol lipase (MAGL) inhibitor J. Med. Chem. 62(4),1932-1958(2019).