CAS NO: | 1101854-58-3 |
规格: | ≥98% |
包装 | 价格(元) |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 520.49 |
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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 | JZL184; JZL 184; JZL-184. |
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. |
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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. |