JZL184

Catalog No.S4904 Batch:S490401

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Technical Data

Formula

C27H24N2O9
Molecular Weight 520.49 CAS No. 1101854-58-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (192.12 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 (from reference)

Kinase Assay:[1]
  • 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 Assay:[2]
  • 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.
Animal Study:[1]
  • Animal Models

    male C57Bl/6 mice

  • Dosages

    4-40 mg/kg

  • Administration

    Intraperitoneally or oral gavage

Selleck's JZL184 has been cited by 8 publications

Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7] PubMed: 35332332
Identification of bioactive natural products using yeast：Application to monoacylglycerol lipase inhibitor extraction from Corydalis Rhizoma [ Biomed Pharmacother, 2022, 149:112798] PubMed: 35286964
Myeloid But Not Endothelial Expression of the CB2 Receptor Promotes Atherogenesis in the Context of Elevated Levels of the Endocannabinoid 2-Arachidonoylglycerol [ J Cardiovasc Transl Res, 2022, 10.1007/s12265-022-10323-z] PubMed: 36178662
Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder [ Open Biol, 2021, 11(2):200306] PubMed: 33529552
Enhanced monoacylglycerol lipolysis by ABHD6 promotes NSCLC pathogenesis. [ EBioMedicine, 2020, 53:102696] PubMed: 32143183
Chlamydia pneumoniae infection-induced endoplasmic reticulum stress causes fatty acid-binding protein 4 secretion in murine adipocytes. [ J Biol Chem, 2020, 295(9):2713-2723] PubMed: 31992597
Lipid accumulation and oxidation in glioblastoma multiforme [ Sci Rep, 2019, 9(1):19593] PubMed: 31863022
p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus [ Elife, 2016, 5e14653] PubMed: 27296803

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.