KML29

Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid receptors. Monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the hydrolysis of 2-AG to arachidonic acid and glycerol, thus terminating its biological function. KML29 is an O-hexafluoroisopropyl carbamate analog of JZL 184 (Item No. 13158) that potently and selectively inhibits MAGL (IC₅₀s = 15, 43, and 5.9 nM in mouse, rat, and human brain proteomes, respectively) over FAAH (IC₅₀s >50 μM).¹ At 5-20 mg/kg, KML29 dose-dependently blocks mouse brain MAGL activity in vivo, without any measurable effect on FAAH activity.¹ As a second generation MAGL inhibitor, KML29 supersedes the low-level cross reactivity that JZL 184 displays for FAAH yet still maintains comparable potency to its parent compound.

WARNING This product is not for human or veterinary use.

1. Chang, J.W., Niphakis, M.J., Lum, K.M., et al. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem. Biol. 19(5), 579-588 (2012).