MK8722 是一种全身性泛 AMPK 激活剂。

MK8722 is an effective and systemic activator of pan-AMPK.

MK8722 is an effective, direct, allosteric activator of all 12 mammalian AMPK complexes. pAMPK activation by maximal AMP plus MK8722 is synergistic, demonstrating that the agents act at distinct sites. MK8722 activates pAMPK complexes with increased potency and magnitude versus AMP (EC50: ~1 to 60 nM) and increased activation by factors of ~4 to 24. Although MK8722 exhibits a higher affinity for β1-containing (~1 to 6 nM) versus β2-containing (~15 to 63 nM) pAMPK complexes, it is the most potent activator of β2 complexes reported to date .

MK8722(once-daily)administration, causes dose-dependent lowering of ambient blood glucose. Chronic MK8722 dosing in mice also increases muscle Glut4 protein levels, possibly contributing to efficacy. Chronic antihyperglycemic efficacy of MK8722 is evaluated in db/db mice (a leptin receptor-deficient T2DM model). Glucose reductions after MK8722 treatment (30 mpk/day) are comparable to those observed with the PPARγ agonist BRL49653 (3 mpk/day), on treatment day 12. Dose-dependent enhances in tissue pACC are maintained throughout the dosing period. Chronic efficacy, without tachyphylaxis, is also observed in additional dysmetabolic and diabetic rodent models. In all cases, efficacy is associated with trough MK8722 plasma levels comparable to the concentrations required to acutely stimulate skeletal muscle glucose uptake. The glucose-lowering action of MK8722 manifests without significant effects on body weight .

1394371-71-1

C24H20ClN3O4

449.89

DMSO:62.5 mg/mL (138.92 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years