MK-3903 is a potent and selective AMPK activator (EC50: 8 nM).

AMPK:8 nM (EC50, cell free)

MK-3903在12种磷酸化AMPK（pAMPK）复合体中激活了10种，其EC50值范围为8至40nM。MK-3903对pAMPK5具有部分激活作用（最大36%），但不激活pAMPK6。MK-3903在LLC-PK1细胞中显示出低渗透性，并且是人肝摄取转运蛋白OATP1B1和OATP1B3（有机阴离子转运蛋白）的底物。MK-3903与前列腺素DP2（CRTH2）受体有中等程度的结合能力（IC50: 1.8 μM），但在含有10%人血清的情况下不绑定（结合IC50>86 μM）。

MK-3903在C57BL/6小鼠、SD大鼠和比格犬中的药代动力学特征表现为中等的系统性血浆清除率（5.0至13 mL/min/kg）、稳态分布容积为0.6至1.1 L/kg，以及终末半衰期约为2小时。在高果糖饲料喂养的db/+小鼠中，MK-3903的急性口服给药（3、10和30 mg/kg）显著抑制了所有三个剂量的肝脏脂肪酸合成（FAS）。

Briefly, the AMPK complex of interest is appropriately diluted in AMPK reaction buffer and incubated at room temperature for 30 min to yield pAMPK. Then, MK-3903 and pAMPK are pre-incubated by adding appropriately diluted MK-3903 in DMSO (1.2 μL total) to the reaction buffer containing pAMPK (15 μL per well), the plate is vortexed briefly and then incubated at room temperature for 30 min. The plate is sealed and incubated at room temperature for 60 min, at which time the reaction is stopped by the addition of quench buffer. EC50s and %activation parameters are calculated from %product vs. activator concentration plots.

DIO mice at 17 weeks of age are used in this study. Mice are conditioned to dosing with vehicle (5% Tween 80, 0.25% methylcellulose, 0.02% SDS) at 5 mL/kg BID for 5 days. At that time, mice are bled, glucose and insulin measured and the animals sorted into treatment groups based on glucose, insulin and body weight. Each group of animals receives the administration of MK-3903 in a vehicle at 3 mg/kg, 10 mg/kg, 30 mg/kg, or vehicle alone for 12-day BID. Another group of mice receiving MK-3903 with the vehicle at 30 mg/kg for 12-day QD is included as well. Food intake and body weight are measured daily.