生物活性 | |||
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描述 | The monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the degradation of 2-arachidonoyl glycerol (2-AG). MJN110 is a potent and selective MAGL inhibitor with an IC50 value of 9.1nM. In human prostate cancer PC3 cells, treatment with MJN110 for 4 hours inhibited MAGL with an IC50 value of ~1nM. MJN110 also potently inhibited the 2-AG hydrolysis of in mouse brain homogenates with an IC50 value of 2.1nM without affecting the hydrolysis of N-arachidonoyl ethanolamine up to 50μM. The oral treatment of MJN110 (0.5–5.0mg/kg) in mice dose-dependently inhibited MAGL expression in the brain and liver. It also inhibited MAGL in vivo when administered intraperitoneally with the maximal inhibition observed at 0.25mg/kg in the live and 1.0mg/kg in the brain. The oral administration of MJN110 led to a 2-fold increase in 2-AG at the dose of 0.5mg/kg and a 10-fold increase at 5.0mg/kg. MJN110-treated mice also showed dose-dependent reduction of arachidonic acid in the brain[1]. | ||
作用机制 | MJN110 inhibits MAGL via the carbamylation of MAGL’s active-site serine nucleophile[1]. |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.16mL 0.43mL 0.22mL |
10.81mL 2.16mL 1.08mL |
21.63mL 4.33mL 2.16mL |
参考文献 |
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