MK-8722

• CAS: 1394371-71-1
• Catalog Number: ACM1394371711
• Category: Activators
• Molecular Weight: 449.89
• Molecular Formula: C24H20ClN3O4
• Description: MK-8722 is a potent pan-AMPK activator. MK-8722 improves glucose homeostasis but induces cardiac hypertrophy. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.
• Synonyms: MK-8722; MK 8722; MK8722
• IUPAC Name: (3R,3aR,6R,6aR)-6-((6-([1,1'-biphenyl]-4-yl)-7-chloro-3H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol
• Canonical SMILES: ClC1=C2C(NC(O[C@@H]3CO[C@@]4([H])[C@]3([H])OC[C@H]4O)=N2)=NC=C1C5=CC=C(C6=CC=CC=C6)C=C5
• InChI: InChI=1S/C24H20ClN3O4/c25-19-16(15-8-6-14(7-9-15)13-4-2-1-3-5-13)10-26-23-20(19)27-24(28-23)32-18-12-31-21-17(29)11-30-22(18)21/h1-10,17-18,21-22,29H,11-12H2,(H,26,27,28)/t17-,18-,21-,22-/m1/s1
• InChI Key: VEGCGBKTFKSLJB-MCEIDBOGSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: MK8722 is a pan-AMPK activator.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 64.07; H, 4.48; Cl, 7.88; N, 9.34; O, 14.22
• Exact Mass: 449.1142
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To determine whether enhanced skeletal muscle glucose uptake underlies the acute glucose-lowering effects of MK-8722, the formation of nonmetabolizable 2-deoxy-D-glucose-6-phosphate (2DG6P), a product of cellular transport and intracellular phosphorylation, was quantified after exposure of cells or tissues to 2-deoxy-D-glucose (2DG) with or without MK-8722. Similar to insulin, MK-8722 treatment of primary human skeletal myocytes, in the absence of insulin, produced a dose-dependent increase in 2DG uptake by as much as a factor of 3 (Fig. 3A). Unlike insulin, MK-8722 treatment significantly increased intracellular pACC, reflective of AMPK activation (Fig. 3A).; Reference: Science. 2017 Aug 4;357(6350):507-511. https://science.sciencemag.org/content/357/6350/507.long
• In Vivo Activity: The effects of MK-8722 on glucose homeostasis were examined in rodents. Remarkably, MK-8722 administration to lean, normoglycemic C57BL/6 mice reduced fasting blood glucose levels 1 hour after dose [immediately prior to the glucose challenge of an intraperitoneal glucose tolerance test (ipGTT)] (Fig. 2, A and B). MK-8722 also improved glucose tolerance during the glucose challenge (Fig. 2, A and C). Elevation of skeletal muscle pACC (14) established systemic AMPK activation by MK-8722 treatment (Fig. 2D). The effects of MK-8722 were dose-dependent. Notably, improved glucose homeostasis using MK-8722 [30 mg/kg (mpk)] was achieved at significantly reduced plasma insulin levels during the ipGTT (Fig. 2E).; Reference: Science. 2017 Aug 4;357(6350):507-511. https://science.sciencemag.org/content/357/6350/507.long
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).