Targets: MAGL
IC50: 9.1 nM
MJN110 is an N-hydroxysuccinimidyl carbamate with great, selective, and in-vivo-active inhibition effect for monoacylglycerol lipase (MAGL) with the IC50 value of 9.1 nM. Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) are biologically active lipids which participate in a mount of synaptic processes. MAGL is a serine hydrolase in charge of the hydrolysis of 2-AG to glycerol and arachidonic acid to terminate its function. And MJN110 could significantly inhibit the hydrolysis of 2-AG with the IC50 value of 2.1 nM without any effect on the hydrolysis of AEA up to 50 μM [1].
In Vitro: In HEK293T cells, MJN110 could inactivate hMAGL with the IC50 value of 9.1 nM, while having no effect on hFAAH activity. Besides, in human prostate cancer cell line PC3 cells which express both MAGL and ABDH6, MJN110 could selectively inhibit MAGL with the IC50 value of ~1 nM and 10-fold over ABDH6 [1].
In Vivo: In a rat model of Diabetic Neuropathy, administrator of MJN110 (5.0 mg·kg-1, i.p.) could alleviate mechanical allodynia by significantly increasing mechanical withdrawal thresholds [1]. Besides, in the mouse chronic constriction injury (CCI) of the sciatic nerve model of neuropathic pain, i.p. administration of MJN110 combined with morphine (the ED50 values of 0.43 mg/kg and 2.4 mg/kg, respectively) could produce opioid-sparing effects with diminished tolerance and cannabimimetic side effects [2].
Clinical trial: No data available.
References:
[1] Niphakis M J, Cognetta A B, Chang J W, et al. Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors.[J]. ACS Chemical Neuroscience, 2013, 4(9): 1322-1332.
[2] Wilkerson J L, Niphakis M J, Grim T W, et al. The selective monoacylglycerol lipase inhibitor MJN110 produces opioid sparing effects in a mouse neuropathic pain model[J]. Journal of Pharmacology and Experimental Therapeutics, 2016, 357(1): 145-156.