1. Epigenetics
    PI3K/Akt/mTOR
  2. AMPK

MK8722 

Cat. No.: HY-111363 Purity: 98.87%
Handling Instructions

MK8722 is a potent and systemic pan-AMPK activator.

For research use only. We do not sell to patients.

MK8722 Chemical Structure

MK8722 Chemical Structure

CAS No. : 1394371-71-1

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MK8722 is a potent and systemic pan-AMPK activator.

IC50 & Target[1]

AMPK

 

In Vitro

MK8722 (MK-8722) is a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. MK8722 activates pAMPK complexes with increased potency and magnitude versus AMP, with EC50 values of ~1 to 60 nM and increased activation by factors of ~4 to 24. Although MK8722 exhibits 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. pAMPK activation by maximal AMP plus MK8722 is synergistic, demonstrating that the agents act at distinct sites[1].

In Vivo

Chronic antihyperglycemic efficacy of MK8722 (MK-8722) is evaluated in db/db mice, a leptin receptor-deficient T2DM model. Once-daily administration of MK8722 results in dose-dependent lowering of ambient blood glucose. On treatment day 12, glucose reductions after MK8722 treatment (30 mpk/day) are comparable to those observed with the PPARγ agonist BRL49653 (3 mpk/day). Unlike BRL49653, the glucose-lowering action of MK8722 manifests without significant effects on body weight, which is a consistent finding. Dose-dependent increases 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. Chronic MK8722 dosing in mice also increases muscle Glut4 protein levels, possibly contributing to efficacy[1].

References
Animal Administration
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

449.89

Formula

C₂₄H₂₀ClN₃O₄

CAS No.

1394371-71-1

SMILES

O[[email protected]]1[[email protected]@]([[email protected]]2([H])OC1)([H])OC[[email protected]]2OC3=NC4=NC(C(C=C5)=CC=C5C6=CC=CC=C6)=C(Cl)C=C4N3

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

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MK8722
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MK8722

Cat. No.: HY-111363