MK-8722 | CAS#1394371-71-1 | pan-AMPK Activator

MedKoo Cat#: 555103 | Name: MK-8722

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

MK-8722

CAS#1394371-71-1

Theoretical Analysis

MedKoo Cat#: 555103

Name: MK-8722

CAS#: 1394371-71-1

Chemical Formula: C24H20ClN3O4

Exact Mass: 449.1142

Molecular Weight: 449.89

Elemental Analysis: C, 64.07; H, 4.48; Cl, 7.88; N, 9.34; O, 14.22

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 3,650.00	Ready to ship

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Related CAS #

No Data

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

More Info

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C21R11B09

View CoA: current batch, Lot#C9R06B04

QC Data

View QC data: current batch, Lot#C21R11B09

View QC data: current batch, Lot#C9R06B04

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	31.3	69.46

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 449.89 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:

In vivo protocol:

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