| Bioactivity | JZL 184 is a potent, selective and irreversible MAGL inhibitor that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis in brain membranes (IC50 of 8 nM). JZL 184 displays >300-fold selectivity for MAGL over FAAH[1][2]. | ||||||||||||
| Target | IC50: 8 nM (2-Arachidonoylglycerol (2-AG) hydrolysis) | ||||||||||||
| Invitro | JZL 184 displays IC50 values of 8 nM and 4 μM for blockade of 2-AG and oleamide (FAAH substrate) hydrolysis in brain membranes, respectively. Comparable inhibitory effects are observed with recombinant MAGL and FAAH when expressed in COS7 cells[1]. | ||||||||||||
| In Vivo | JZL 184 (4-40 mg/kg; intraperitoneal injection; once; C57Bl/6 mice) treatment produces a rapid and sustained blockade of brain 2-AG hydrolase activity in mice, resulting in 8-fold elevations in endogenous 2-AG levels that are maintained for at least 8 h. JZL 184-treated mice shows a remarkable array of CB1-dependent behavioral effects, including analgesia, hypomotility, and hypothermia[1].JZL 184 prolongs depolarization-induced suppression of excitation (DSE) in Purkinje neurons in cerebellar slices and DSE inhibition (DSI) in CA1 pyramidal neurons in hippocampal slices. JZL 184 produces greater enhancement of DSE/DSI in mouse neurons than that in rat neurons[2]. Animal Model: | ||||||||||||
| Name | JZL 184 | ||||||||||||
| CAS | 1101854-58-3 | ||||||||||||
| Formula | C27H24N2O9 | ||||||||||||
| Molar Mass | 520.49 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Long JZ, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44. [2]. Pan B, et al. Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) Enhances retrograde endocannabinoid signaling. J Pharma |