WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555103
CAS#: 1394371-71-1
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.
MedKoo Cat#: 555103
Name: MK-8722
CAS#: 1394371-71-1
Chemical Formula: C24H20ClN3O4
Exact Mass: 449.1142
Molecular Weight: 449.891
Elemental Analysis: C, 64.07; H, 4.48; Cl, 7.88; N, 9.34; O, 14.22
Synonym: MK-8722; MK 8722; MK8722.
IUPAC/Chemical 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
InChi Key: VEGCGBKTFKSLJB-MCEIDBOGSA-N
InChi Code: 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
SMILES Code: 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | MK8722 is a pan-AMPK activator. |
| 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 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 31.25 | 69.46 |
The following data is based on the product molecular weight 449.891 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Myers RW, Guan HP, Ehrhart J, Petrov A, Prahalada S, Tozzo E, Yang X, Kurtz MM, Trujillo M, Gonzalez Trotter D, Feng D, Xu S, Eiermann G, Holahan MA, Rubins D, Conarello S, Niu X, Souza SC, Miller C, Liu J, Lu K, Feng W, Li Y, Painter RE, Milligan JA, He H, Liu F, Ogawa A, Wisniewski D, Rohm RJ, Wang L, Bunzel M, Qian Y, Zhu W, Wang H, Bennet B, LaFranco Scheuch L, Fernandez GE, Li C, Klimas M, Zhou G, van Heek M, Biftu T, Weber A, Kelley DE, Thornberry N, Erion MD, Kemp DM, Sebhat IK. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy. Science. 2017 Aug 4;357(6350):507-511. doi: 10.1126/science.aah5582. Epub 2017 Jul 13. PMID: 28705990. 2. Zhou X, Muise ES, Haimbach R, Sebhat IK, Zhu Y, Liu F, Souza SC, Kan Y, Pinto S, Kelley DE, Hoek M. PAN-AMPK Activation Improves Renal Function in a Rat Model of Progressive Diabetic Nephropathy. J Pharmacol Exp Ther. 2019 Oct;371(1):45-55. doi: 10.1124/jpet.119.258244. Epub 2019 Jul 12. PMID: 31300612. |
| In vitro protocol: | 1. Myers RW, Guan HP, Ehrhart J, Petrov A, Prahalada S, Tozzo E, Yang X, Kurtz MM, Trujillo M, Gonzalez Trotter D, Feng D, Xu S, Eiermann G, Holahan MA, Rubins D, Conarello S, Niu X, Souza SC, Miller C, Liu J, Lu K, Feng W, Li Y, Painter RE, Milligan JA, He H, Liu F, Ogawa A, Wisniewski D, Rohm RJ, Wang L, Bunzel M, Qian Y, Zhu W, Wang H, Bennet B, LaFranco Scheuch L, Fernandez GE, Li C, Klimas M, Zhou G, van Heek M, Biftu T, Weber A, Kelley DE, Thornberry N, Erion MD, Kemp DM, Sebhat IK. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy. Science. 2017 Aug 4;357(6350):507-511. doi: 10.1126/science.aah5582. Epub 2017 Jul 13. PMID: 28705990. |
| In vivo protocol: | 1. Myers RW, Guan HP, Ehrhart J, Petrov A, Prahalada S, Tozzo E, Yang X, Kurtz MM, Trujillo M, Gonzalez Trotter D, Feng D, Xu S, Eiermann G, Holahan MA, Rubins D, Conarello S, Niu X, Souza SC, Miller C, Liu J, Lu K, Feng W, Li Y, Painter RE, Milligan JA, He H, Liu F, Ogawa A, Wisniewski D, Rohm RJ, Wang L, Bunzel M, Qian Y, Zhu W, Wang H, Bennet B, LaFranco Scheuch L, Fernandez GE, Li C, Klimas M, Zhou G, van Heek M, Biftu T, Weber A, Kelley DE, Thornberry N, Erion MD, Kemp DM, Sebhat IK. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy. Science. 2017 Aug 4;357(6350):507-511. doi: 10.1126/science.aah5582. Epub 2017 Jul 13. PMID: 28705990. 2. Zhou X, Muise ES, Haimbach R, Sebhat IK, Zhu Y, Liu F, Souza SC, Kan Y, Pinto S, Kelley DE, Hoek M. PAN-AMPK Activation Improves Renal Function in a Rat Model of Progressive Diabetic Nephropathy. J Pharmacol Exp Ther. 2019 Oct;371(1):45-55. doi: 10.1124/jpet.119.258244. Epub 2019 Jul 12. PMID: 31300612. |
1: Weihrauch M, Handschin C. Pharmacological targeting of exercise adaptations in
skeletal muscle: Benefits and pitfalls. Biochem Pharmacol. 2017 Oct 20. pii:
S0006-2952(17)30636-6. doi: 10.1016/j.bcp.2017.10.006. [Epub ahead of print]
Review. PubMed PMID: 29061342.
2: Myers RW, Guan HP, Ehrhart J, Petrov A, Prahalada S, Tozzo E, Yang X, Kurtz
MM, Trujillo M, Gonzalez Trotter D, Feng D, Xu S, Eiermann G, Holahan MA, Rubins
D, Conarello S, Niu X, Souza SC, Miller C, Liu J, Lu K, Feng W, Li Y, Painter RE,
Milligan JA, He H, Liu F, Ogawa A, Wisniewski D, Rohm RJ, Wang L, Bunzel M, Qian
Y, Zhu W, Wang H, Bennet B, LaFranco Scheuch L, Fernandez GE, Li C, Klimas M,
Zhou G, van Heek M, Biftu T, Weber A, Kelley DE, Thornberry N, Erion MD, Kemp DM,
Sebhat IK. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but
induces cardiac hypertrophy. Science. 2017 Aug 4;357(6350):507-511. doi:
10.1126/science.aah5582. Epub 2017 Jul 13. PubMed PMID: 28705990.
3. Discovery of MK-8722: A Systemic, Direct Pan-Activator of AMP-Activated Protein Kinase
Danqing Feng, Tesfaye Biftu, F. Anthony Romero, Ahmet Kekec, James Dropinski, Andrew Kassick, Shiyao Xu, Marc M. Kurtz, Anantha Gollapudi, Qing Shao, Xiaodong Yang, Ku Lu, Gaochao Zhou, Daniel Kemp, Robert W. Myers, Hong-Ping Guan, Maria E. Trujillo, Cai Li, Ann Weber, and Iyassu K. Sebhat
Publication Date (Web): December 1, 2017 (Letter)
DOI: 10.1021/acsmedchemlett.7b00417
5′-Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of mammalian energy
homeostasis and has been implicated in mediating many of the beneficial effects of exercise and weight loss including lipid and
glucose trafficking. As such, the enzyme has long been of interest as a target for the treatment of Type 2 Diabetes Mellitus.
