URB602 is a specific monoacylglycerol lipase (MGL) inhibitor, which inhibits rat brain MGL (IC50: 28±4 μM) through a noncompetitive mechanism.

MGL:28±4 μM

MGL对2-AG的表观Km值为24±1.7 μM，其Vmax为1814±51 nmol/min/mg蛋白；在URB602作用下，Km值为20±0.4 μM，Vmax为541±20 nmol/min/mg蛋白（n=4）。将大鼠前脑的器官型切片培养体与URB602（100 μM）一同孵育时，基线以及Ca2+-离子载体刺激下的2-花生四烯酰基甘油（2-AG）浓度均有所增加[1]。URB602通过快速且非竞争性机制弱抑制重组MGL（IC50：223±63 μM）。

URB602（20-40 mg/kg）能减缓上消化道传输速度和降低结肠推进力。在全肠道传输实验中，URB602剂量依赖性地抑制传输速率（P<0.05），与对照组相比有显著差异。然而，在特定小鼠中，40 mg/kg的URB602对全肠道传输的抑制作用消失，这表明CB1受体在其抑制作用中起着重要作用[3]。在福尔马林试验的早期阶段，URB602减少了成年雄性斯普拉格-道利大鼠JZL184（ED50: 0.06±0.028 μg）和URB602（ED50: 120±51.3 μg）的疼痛行为面积下曲线（AUC）。同时，两种MGL抑制剂在福尔马林疼痛的晚期也能抑制疼痛行为，分别为JZL184（ED50: 0.03±0.011 μg）和URB602（ED50: 66±23.9 μg）。

Samples containing either URB602 (300 μM), MGL (1.4 pM), or both URB602 and MGL are incubated at 37°C for 30 min in assay buffer. At various time points, the reaction is stopped with an equal volume of ice-cold methanol and directly analyzed in positive ionization mode by LC/MS. A SB-CN column (150×2.1 mm i.d., 5 μm) eluted is used with a linear gradient of methanol in water containing 0.25% acetic acid and 5 mM ammonium acetate (from 60% to 100% of methanol in 8 min) at a flow rate of 0.5 mL/min with column temperature at 50°C. Capillary voltage is set at 4 kV and fragmentor voltage is 100V. Nebulizer pressure is set at 60 psi. N2 is used as drying gas at a flow rate of 13 liters/min and a temperature of 350°C. ESI is in the positive mode and a full scan spectrum is acquired from m/z 100 to 600. Extracted ion chromatograms are used to quantify URB602 ([M+H]+, m/z 296)[2].