MK-3903

MK-3903 is a potent AMPK activator with EC50 value of 9nM and max AMP activation of 320%. MK-3903 exhibited effect on recombinant human pAMPK complexes α1 β1 γ1, α1 β1 γ2, α1 β1 γ3, α1 β2 γ1, α1 β2 γ2, α1 β2 γ3, α2 β1 γ1, α2 β1 γ2, α2 β1 γ3, α2 β2 γ1, α2 β2 γ2 and α2 β2 γ3 units with EC50 value/max (%) of 8nM/217%, 21nM/242%, 19nM/61%, 40nM/50%, 118nM/36%, 2860nM/8%, 9nM/320%, 22nM/175%, 26nM/209%, 39nM/94%, 23nM/145% and 35nM/135%, respectively. Oral administration of MK-3903 at dose of 30mg/kg, BID, for 15days significantly increased the level of phosphorylated ACC, a downstream AMPK substrate as an indicator of intracellular AMPK activation, in liver and muscle of diet-induced obese mice. The hepatic fatty acid synthesis was inhibited by 29%, 37% and 49% in db/+mice dosed of 3, 10 and 30mg/kg MK-3903 post 8h. Oral dose of 10 and 30mg/kg MK-3903, BID, for 12 days resulted reduction of insulin resistance index of diet-induced obese mice up to 35% and 64% in an oral glucose tolerance test.

溶解方案(细胞实验)

DMSO 中的溶解度 : ≥ 100 mg/mL (219.83 mM; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|* "≥" means soluble, but saturation unknown.

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (5.50 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (5.50 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"