JZL184

Catalog No.S4904

JZL184 Chemical Structure

Molecular Weight(MW): 520.49

JZL 184 is the first selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 8 nM.

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Biological Activity

Description JZL 184 is the first selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 8 nM.
Targets
MAGL [1]
8 nM
In vitro

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. [1]

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. [1]

Protocol

Kinase Assay:[1]
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activity-based protein profiling (ABPP):

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 s
Cell Research:[2]
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  • Cell lines: LOVO, Caco-2, SW480
  • Concentrations: 0.5 μg/μL
  • Incubation Time: 24 h
  • Method: 1 × 105 cells 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: male C57Bl/6 mice
  • Formulation: 4:1 v/v PEG300/Tween80
  • Dosages: 4-40 mg/kg
  • Administration: Intraperitoneally or oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (192.12 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 520.49
Formula

C27H24N2O9

CAS No. 1101854-58-3
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID