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 (Cay-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). At 5-20 mg/kg, KML29 dose-dependently blocks mouse brain MAGL activity in vivo, without any measurable effect on FAAH activity. 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.Formal Name: 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate. CAS Number: 1380424-42-9. Molecular Formula: C24H21F6NO7. Formula Weight: 549.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 2 mg/ml. lambdamax: 205, 287 nm. SMILES: O=C(OC(C(F)(F)F)C(F)(F)F)N1CCC(C(C2=CC=C(OCO3)C3=C2)(O)C4=CC(OCO5)=C5C=C4)CC1. InChi Code: InChI=1S/C24H21F6NO7/c25-23(26,27)20(24(28,29)30)38-21(32)31-7-5-13(6-8-31)22(33,14-1-3-16-18(9-14)36-11-34-16)15-2-4-17-19(10-15)37-12-35-17/h1-4,9-10,13,20,33H,5-8,11-12H2. InChi Key: SXHQLPHDBLTFPM-UHFFFAOYSA-N. License: Sold under license from The Scripps Research Institute..