MK-8722 is a potent, direct, allosteric activator of all 12 mammalian pan-AMPK complexes.
MK-8722 is a potent, direct, allosteric activator of all 12 mammalian pan-AMPK complexes.
MK-8722 activates pAMPK complexes with increased potency and magnitude versus AMP. In primary mouse hepatocytes, HepG2 cells, or primary human myocytes, MK-8722 results in the phosphorylation of a number of additional known targets of pAMPK, and the most potent off-target activity observed for MK8722 is against the serotonin 5-HT2A receptor.[1]
Pharmacological pan-AMPK activation by MK-8722 leads to chronically sustainable improvements in glucose homeostasis, including the amelioration of insulin resistance and hyperglycemia. Acute treatment with MK-8722 (30 mpk) significantly suppress blood glucose and insulin levels. In mice, chronic MK-8722 dose also increases muscle Glut4 protein levels. In rhesus monkeys, MK8722 results in cardiac hypertrophy associated with increased cardiac and skeletal muscle glycogen.[1]
[1] Robert W Myers, et al. Science . 2017 Aug 4;357(6350):507-511.
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Animal experiment: |
Mice[1]Housing Lean C57BL/6 mice at 10-12 weeks of age and C57BL/6 eDIO mice at 16 weeks of age are used. db/db mice at 7 weeks of age are used. Animals are maintained on a 12 hr/12 hr light-dark cycle with free access to food and water with the temperature maintained at 22oC. Four lean C57BL/6 mice are housed in a standard cage. eDIO mice are individually caged. Eight db/db mice are housed in a large rodent cage. C57BL/6 mice and db/db mice are maintained on regular rodent chow diet 7012 (5% dietary fat; 3.75 kcal/g) for 1-2 weeks before receiving compound treatments. eDIO mice are maintained on 60% kcal% fat diet. Oral dosing of MK8722 in standard vehicle, or vehicle alone, is performed using 10 mL/kg body weight. The effect of MK8722 on various metabolic parameters is established by comparison to vehicle treated animals[1]. |
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参考文献: [1]. Myers RW, et al. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiachypertrophy. Science. 2017 Aug 4;357(6350):507-511. |
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