JZL184

製品コードS4904 バッチS490404

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H24N2O9
分子量 520.49 CAS No. 1101854-58-3
Solubility (25°C)* 体外 DMSO 100 mg/mL (192.12 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 JZL 184 is the first selective inhibitor of monoacylglycerol lipase (MAGL) with IC50 of 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]

プロトコル(参考用のみ)

キナーゼアッセイ 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
細胞アッセイ 細胞株 LOVO, Caco-2, SW480
濃度 0.5 μg/μL
反応時間 24 h
実験の流れ 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.
動物実験 動物モデル male C57Bl/6 mice
投薬量 4-40 mg/kg
投与方法 Intraperitoneally or oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。