| Bioactivity | KML29 is an extremely selective, orally active and irreversible MAGL inhibitor, with IC50 values of 15 nM, 43 nM and 5.9 nM for mouse, rat and human MAGL, respectively. KML29 exhibits minimal cross-reactivity toward other central and peripheral serine hydrolases, including no detectable activity against FAAH[1][2]. | ||||||||||||
| Target | IC50: 15 nM (mouse MAGL), 43 nM (rat MAGL), 5.9 nM (human MAGL). | ||||||||||||
| Invitro | KML29 dose-dependently elevates brain 2-AG level up to 10-fold without alteration in brain levels of anandamide, palmitoylethanolamide, and oleoylethanolamide[2].KML29 is a potent inhibitor of 2-AG hydrolysis, but did not affect AEA hydrolysis at any concentration tested[2]. | ||||||||||||
| In Vivo | KML29 enhibits antinociceptive activity without cannabimimetic side effects[3].KML29 (20 mg/kg) has a significant but modest protective effect against LPS-induced fever[3]. Animal Model: | ||||||||||||
| Name | KML29 | ||||||||||||
| CAS | 1380424-42-9 | ||||||||||||
| Formula | C24H21F6NO7 | ||||||||||||
| Molar Mass | 549.42 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Natsuo Ueda, et al. Discrimination between two endocannabinoids. Chem Biol. 2012 May 25;19(5):545-7. [2]. Jae Won Chang, et al. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem Biol. 2012 May 25;19(5):579-88. [3]. B M Ignatowska-Jankowska, et al. In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects. Br J Pharmacol. 2014 Mar;171(6):1392-407. |