product name JZL184
Description: JZL 184 is the first selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 8 NM. JZL184 is a useful tool for studying the effects of endogenous 2-AG signaling. JZL184 displays time-dependent inhibition of MAGL and exhibits >300-fold selectivity for MAGL over FAAH in vitro. JZL184 does not interact with CB1 or CB2 receptors and does not inhibit the 2-AG biosynthetic enzymes diacylglycerol lipase-αand diacylglycerol lipase-β, or the arachidonic acid–mobilizing enzyme cytosolic phospholipase A2 group IVA.
References: Nat Chem Biol. 2009 Jan;5(1):37-44; Cancer Lett. 2011 Aug 1;307(1):6-17.
520.49
Formula
C27H24N2O9
CAS No.
1101854-58-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (192.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% Propylene glycol: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: JZL184 is a useful tool for studying the effects of endogenous 2-AG signaling. JZL184 displays time-dependent inhibition of MAGL and exhibits >300-fold selectivity for MAGL over FAAH in vitro. JZL184 does not interact with CB1 or CB2 receptors and does not inhibit the 2-AG biosynthetic enzymes diacylglycerol lipase-αand diacylglycerol lipase-β, or the arachidonic acid–mobilizing enzyme cytosolic phospholipase A2 group IVA. Kinase Assay: Mouse brains are Dounce-homogenized in PBS, pH7.5, followed by a low-speed spin (1,400×, 5 min) to remove debris. The supernatant is then subjected to centrifugation (64,000×, 45 min) to provide the cytosolic fraction in the supernatant and the membrane fraction as a pellet. The pellet is washed and resuspended in PBS buffer by sonication. Total protein concentration in each fraction is determined using a protein assay kit. Samples are stored at -80 °C until use. Mouse brain membrane proteomes, are diluted to 1 mg/mL in PBS and pre-incubated with varying concentrations of inhibitors (1 nM to 10 mM) for 30 min at 37 °C before the addition of FP-rhodamine at a final concentration of 2 mM in a 50 mL total reaction volume. After 30 min at 25 °C, the reactions are quenched with 4×SDS-PAGE loading buffer, boiled for 5 min at 90 °C, subjected to SDS-PAGE and visualized in-gel using a flatbed fluorescence scanner. Cell Assay: 1 × 105 cells (LOVO, Caco-2, SW480) are split into four-well chamber slides and incubated with culture medium containing BrdU for 4 h. BrdU staining is performed following the manufacturer’s instructions. |
|---|---|
| In Vivo | JZL184 produced a rapid and sustained blockade of brain 2-AG hydrolase activity in mice, resulting in eight-fold elevations in endogenous 2-AG levels that are maintained for at least 8 h. JZL184-treated mice showed a wide array of CB1-dependent behavioral effects, including analgesia, hypomotility and hypothermia, that suggest a broad role for 2-AG–mediated endocannabinoid signaling throughout the mammalian nervous system. |
| Animal model | Male C57Bl/6 mice |
| Formulation & Dosage | Formulated in 4:1 v/v PEG300/Tween80; 4-40 mg/kg; Intraperitoneally or oral gavage |
| References | Nat Chem Biol. 2009 Jan;5(1):37-44; Cancer Lett. 2011 Aug 1;307(1):6-17. |
