A-769662
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 401018

CAS#: 844499-71-4

Description: A-769662 is a potent, reversible AMP-activated protein kinase (AMPK) activator with an EC50 of 0.8 μM.A-769662 displays selectivity towards β1 subunit-containing heterotrimers.


Price and Availability

Size
Price

100mg
USD 750
1g
USD 3250
Size
Price

200mg
USD 1350
Size
Price

500mg
USD 1950

A-769662, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 401018
Name: A-769662
CAS#: 844499-71-4
Chemical Formula: C20H12N2O3S
Exact Mass: 360.05686
Molecular Weight: 360.38588
Elemental Analysis: C, 66.65; H, 3.36; N, 7.77; O, 13.32; S, 8.90


Synonym: A769662; A 769662; A-769662

IUPAC/Chemical Name: 4-hydroxy-3-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile

InChi Key: CTESJDQKVOEUOY-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H12N2O3S/c21-9-14-18(24)17-15(10-26-20(17)22-19(14)25)12-7-5-11(6-8-12)13-3-1-2-4-16(13)23/h1-8,10,23H,(H2,22,24,25)

SMILES Code: N#CC1=C(O)C(C(C2=CC=C(C3=CC=CC=C3O)C=C2)=CS4)=C4NC1=O


Technical Data

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, not in water

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).

Harmonized System Code:
293490


Additional Information

A-769662 is a new activator of AMP-activated protein kinase (AMPK). Unlike other pharmacological activators, it directly activates native rat AMPK by mimicking both effects of AMP, i.e. allosteric activation and inhibition of dephosphorylation. It was found that it has no effect on the isolated alpha subunit kinase domain, with or without the associated autoinhibitory domain, or on interaction of glycogen with the beta subunit glycogen-binding domain. Although it mimics actions of AMP, it has no effect on binding of AMP to the isolated Bateman domains of the gamma subunit. The addition of A-769662 to mouse embryonic fibroblasts or primary mouse hepatocytes stimulates phosphorylation of acetyl-CoA carboxylase (ACC), effects that are completely abolished in AMPK-alpha1(-/-)alpha2(-/-) cells but not in TAK1(-/-) mouse embryonic fibroblasts. Phosphorylation of AMPK and ACC in response to A-769662 is also abolished in isolated mouse skeletal muscle lacking LKB1, a major upstream kinase for AMPK in this tissue. However, in HeLa cells, which lack LKB1 but express the alternate upstream kinase calmodulin-dependent protein kinase kinase-beta, phosphorylation of AMPK and ACC in response to A-769662 still occurs. These results show that in intact cells, the effects of A-769662 are independent of the upstream kinase utilized.  (see: Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, Viollet B, Hardie DG, Sakamoto K. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 2007 Nov 9;282(45):32549-60. http://www.ncbi.nlm.nih.gov/pubmed/17855357)

 
 


References

  1: Liu XM, Peyton KJ, Shebib AR, Wang H, Korthuis RJ, Durante W. Activation of AMPK stimulates heme oxygenase-1 gene expression and human endothelial cell survival. Am J Physiol Heart Circ Physiol. 2010 Oct 29. [Epub ahead of print] PubMed PMID: 21037234.

2: Leclerc I, Sun G, Morris C, Fernandez-Millan E, Nyirenda M, Rutter GA. AMP-activated protein kinase regulates glucagon secretion from mouse pancreatic alpha cells. Diabetologia. 2011 Jan;54(1):125-34. Epub 2010 Oct 13. PubMed PMID: 20938634.

3: Santidrián AF, González-Gironès DM, Iglesias-Serret D, Coll-Mulet L, Cosialls AM, de Frias M, Campàs C, González-Barca E, Alonso E, Labi V, Viollet B, Benito A, Pons G, Villunger A, Gil J. AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood. 2010 Oct 21;116(16):3023-32. Epub 2010 Jul 27. PubMed PMID: 20664053.

4: Rajamohan F, Harris MS, Frisbie RK, Hoth LR, Geoghegan KF, Valentine JJ, Reyes AR, Landro JA, Qiu X, Kurumbail RG. Escherichia coli expression, purification and characterization of functional full-length recombinant alpha2beta2gamma3 heterotrimeric complex of human AMP-activated protein kinase. Protein Expr Purif. 2010 Oct;73(2):189-97. Epub 2010 May 6. PubMed PMID: 20451617.

5: Sid B, Miranda L, Vertommen D, Viollet B, Rider MH. Stimulation of human and mouse erythrocyte Na(+)-K(+)-2Cl(-) cotransport by osmotic shrinkage does not involve AMP-activated protein kinase, but is associated with STE20/SPS1-related proline/alanine-rich kinase activation. J Physiol. 2010 Jul 1;588(Pt 13):2315-28. Epub 2010 May 4. PubMed PMID: 20442269; PubMed Central PMCID: PMC2915509.

6: Miranda L, Carpentier S, Platek A, Hussain N, Gueuning MA, Vertommen D, Ozkan Y, Sid B, Hue L, Courtoy PJ, Rider MH, Horman S. AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells. Biochem Biophys Res Commun. 2010 Jun 4;396(3):656-61. Epub 2010 May 8. PubMed PMID: 20438708.

7: Sopjani M, Bhavsar SK, Fraser S, Kemp BE, Föller M, Lang F. Regulation of Na+-coupled glucose carrier SGLT1 by AMP-activated protein kinase. Mol Membr Biol. 2010 Apr;27(2-3):137-44. PubMed PMID: 20334581.

8: Fazakerley DJ, Holman GD, Marley A, James DE, Stöckli J, Coster AC. Kinetic evidence for unique regulation of GLUT4 trafficking by insulin and AMP-activated protein kinase activators in L6 myotubes. J Biol Chem. 2010 Jan 15;285(3):1653-60. Epub 2009 Nov 13. PubMed PMID: 19915010; PubMed Central PMCID: PMC2804323.

9: García-García C, Fumarola C, Navaratnam N, Carling D, López-Rivas A. AMPK-independent down-regulation of cFLIP and sensitization to TRAIL-induced apoptosis by AMPK activators. Biochem Pharmacol. 2010 Mar 15;79(6):853-63. Epub 2009 Nov 5. PubMed PMID: 19896469.

10: Fujimoto A, Akifusa S, Kamio N, Hirofuji T, Nonaka K, Yamashita Y. Involvement of mTOR in globular adiponectin-induced generation of reactive oxygen species. Free Radic Res. 2010 Feb;44(2):128-34. PubMed PMID: 19886750.