JNJ-42226314 demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol (2-AG) as well as efficacy in models of neuropathic and inflammatory pain. JNJ-42226314 is a competitive, highly selective and reversible non-covalent monoacylglycerol lipase (MAGL) inhibitor.

JNJ-42226314 has IC50s of 1.13 nM, 1.88 nM, 0.67 nM, 0.97 nM for human Hela cells, human PBMC, mouse brain and rat brain, respectively.

JNJ-42226314 (i.p.; 30 mg/kg) is antinociceptive in the rat complete Freund's adjuvant (CFA) model of inflammatory pain. JNJ-42226314 has t1/2 values of 11.4, 27.6, 27.2 min for MAGL in human, mouse and rat, respectively. JNJ-42226314 (i.p.; 3 mg/kg and 30 mg/kg; 120 min) dose-dependently elevates hippocampal 2-AG in vivo. JNJ-42226314 (i.p.; 30 mg/kg)significantly increases total wake time for up to 8 hours afterward, whereas total wake time was only elevated for 2 hr following a 3 mg/kg dose.

1252765-13-1

C26H24FN5O2S

489.56

JNJ-42226314

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years