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JZL184

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Chemical Structure| 1101854-58-3 同义名 : -
CAS号 : 1101854-58-3
货号 : A513618
分子式 : C27H24N2O9
纯度 : 98%
分子量 : 520.49
MDL号 : MFCD11976911
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(67.24 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5%DMSO+40%PEG300+5%Tween80+water 2.5 mg/mL

生物活性
靶点

  • Lipase

    MAGL, IC50:8 nM
描述 Monoacylglycerol lipase (MAGL) is a key enzyme in the human endocannabinoid system. It is also the main enzyme responsible for the conversion of 2-arachidonoyl glycerol (2-AG) to arachidonic acid (AA), a precursor of prostaglandin synthesis. The inhibition of MAGL activity would be beneficial for the treatment of a wide range of diseases, such as inflammation, neurodegeneration, metabolic disorders and cancer[3]. JZL 184 is a potent, selective and irreversible MAGL inhibitor that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis in brain membranes (IC50 of 8 nM). JZL 184 displays >300-fold selectivity for MAGL over FAAH. JZL 184 displays IC50 values of 8 nM and 4 μM for blockade of 2-AG and oleamide (FAAH substrate) hydrolysis in brain membranes, respectively. Comparable inhibitory effects are observed with recombinant MAGL and FAAH when expressed in COS7 cells. JZL 184 (4-40 mg/kg; intraperitoneal injection; once; C57Bl/6 mice) treatment produces a rapid and sustained blockade of brain 2-AG hydrolase activity in mice, resulting in 8-fold elevations in endogenous 2-AG levels that are maintained for at least 8 h. JZL 184-treated mice shows a remarkable array of CB1-dependent behavioral effects, including analgesia, hypomotility, and hypothermia[4]. 8 mg/kg JZL-184 significantly increased the levels of 2-AG in the auditory cortex of both Fmr1 KO and WT mice 4 h post-treatment. A reduction in the abnormally enhanced baseline gamma-band power in Fmr1 KO mice and significantly improved evoked synchronization to auditory stimuli in the gamma-band range post-JZL-184 treatment. JZL-184 treatment also ameliorated anxiety-like and hyperactivity phenotypes in Fmr1 KO mice[5]. JZL 184 prolongs depolarization-induced suppression of excitation (DSE) in Purkinje neurons in cerebellar slices and DSE inhibition (DSI) in CA1 pyramidal neurons in hippocampal slices. JZL 184 produces greater enhancement of DSE/DSI in mouse neurons than that in rat neurons[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
COS7 cells Function assay Inhibition of human MAGL expressed in monkey COS7 cells, IC50=0.002 μM 23455058
COS7 cells Function assay Inhibition of human MAGL expressed in COS7 cells using endogenous 2-AG substrate, IC50=0.002 μM 22738638
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.61mL

1.92mL

0.96mL

19.21mL

3.84mL

1.92mL
参考文献

[1]Schlosburg JE, Kinsey SG, et al. Prolonged monoacylglycerol lipase blockade causes equivalent cannabinoid receptor type 1 receptor-mediated adaptations in fatty acid amide hydrolase wild-type and knockout mice. J Pharmacol Exp Ther. 2014 Aug;350(2):196-204.

[2]Long JZ, Li W, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44.

[3]Ziad Omran. New Disulfiram Derivatives as MAGL-Selective Inhibitors. Molecules. 2021 May 30;26(11):3296.

[4] Long JZ, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44.

[5] Patricia S Pirbhoy, Carrie R Jonak,et al. Increased 2-arachidonoyl-sn-glycerol levels normalize cortical responses to sound and improve behaviors in Fmr1 KO mice. J Neurodev Disord. 2021 Oct 13;13(1):47.

[6]Pan B, et al. Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) Enhances retrograde endocannabinoid signaling. J Pharmacol Exp Ther. 2009 Nov;331(2):591-7.