A 769662

Catalog # Availability Size / Price Qty
A 769662 | CAS No. 844499-71-4 | AMPK Activators
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Description: Potent AMPK activator

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

Purity: ≥98%

Product Details
Citations (24)
Supplemental Products

Biological Activity

A 769662 is a potent, reversible AMP-activated protein kinase (AMPK) activator (EC50 = 0.8 μM) that displays selectivity towards β1 subunit-containing heterotrimers. Inhibits fatty acid synthesis (IC50 = 3.2 μM) and decreases plasma glucose and triglyceride levels in vivo. Also inhibits proliferation of mesenchymal stem cells, and impedes reprogramming of mouse embryonic fibroblasts to iPSCs. Activates autophagy.

Technical Data

Soluble to 100 mM in DMSO
Store at +4°C

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

  1. The AMP-Dependent Protein Kinase (AMPK) Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation
    Y Huang, CA Smith, G Chen, B Sharma, AS Miner, RW Barbee, PH Ratz
    Front Pharmacol, 2017;8(0):756.
  2. AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation
    R Gélinas, F Mailleux, J Dontaine, L Bultot, B Demeulder, A Ginion, EP Daskalopou, H Esfahani, E Dubois-Der, B Lauzier, C Gauthier, AK Olson, B Bouchard, C Des Rosier, B Viollet, K Sakamoto, JL Balligand, JL Vanoversch, C Beauloye, S Horman, L Bertrand
    Nat Commun, 2018;9(1):374.
  3. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.
    Jenkins Y, Sun T, Markovtsov V, Foretz M, Li W, Nguyen H, Li Y, Pan A, Uy G, Gross L, Baltgalvis K, Yung S, Gururaja T, Kinoshita T, Owyang A, Smith I, McCaughey K, White K, Godinez G, Alcantara R, Choy C, Ren H, Basile R, Sweeny D, Xu X, Issakani S, Carroll D, Goff D, Shaw S, Singh R, Boros L, Laplante M, Marcotte B, Kohen R, Viollet B, Marette A, Payan D, Kinsella T, Hitoshi Y
    PLoS ONE, 2013;8(12):e81870.
  4. The Role of O-GlcNAcylation in Perivascular Adipose Tissue Dysfunction of Offspring of High-Fat Diet-Fed Rats
    KE Zaborska, G Edwards, C Austin, M Wareing
    J. Vasc. Res., 2017;54(2):79-91.
  5. Sirtuin 1 Is a Key Regulator of the Interleukin-12 p70/Interleukin-23 Balance in Human Dendritic Cells.
    Alvarez Y, Rodriguez M, Municio C, Hugo E, Alonso S, Ibarrola N, Fernandez N, Crespo M
    J Biol Chem, 2012;287(42):35689-701.
  6. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

    Circ Res, 2016;0(0):.
  7. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells.
    Lanna, Alessio, Henson, Sian M, Escors, David, Akbar, Arne N
    Nat Immunol, 2014;15(10):965-72.
  8. Role of AMP-activated protein kinase in regulating hypoxic survival and proliferation of mesenchymal stem cells.
    de Meester et al.
    Cardiovasc.Res., 2014;101:20
  9. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles.
    Galluzzi et al.
    Nat.Rev.Drug.Discov., 2017;
  10. Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells.
    Vazquez-Martin et al.
    Cell Cycle, 2012;5:974
  11. MetF. activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats.
    Duca et al.
    Nat.Med., 2015;21:506
  12. Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family.
    Sanders et al.
    J.Biol.Chem., 2007;282:32539
  13. Thienopyridone drugs are selective activators of AMP-activated protein kinase β1-containing complexes.
    Scott et al.
    Chem.Biol., 2008;15:1220
  14. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome.
    Cool et al.
    Cell Met., 2006;3:403

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Citations for A 769662

The citations listed below are publications that use Tocris products. Selected citations for A 769662 include:

24 Citations: Showing 1 - 10

  1. Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965.
    Authors: Ahwazi Et al.
    Biochem J  2021;478:2977
  2. AMPK activation regulates P-body dynamics in mouse sensory neurons in vitro and in vivo.
    Authors: Paige Et al.
    Neurobiol Pain  2019;5
  3. Peroxisome Proliferator-Activated Receptor α Agonist and Its Target Nanog Cooperate to Induce Pluripotency.
    Authors: Lee Et al.
    J Clin Med  2018;7
  4. Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: IMPLICATIONS FOR AMP KINASE.
    Authors: Mahapatra Et al.
    J Biol Chem  2017;292:64
  5. Entosis Is Induced by Glucose Starvation.
    Authors: Hamann Et al.
    Cell Rep  2017;20:201
  6. Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK.
    Authors: Dai Et al.
    Autophagy  2017;13:1435
  7. AMP-activated protein kinase activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner.
    Authors: Vlachaki Walker Et al.
    Diabetes Obes.Metab.  2017;
  8. mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells.
    Authors: Saric Et al.
    Arterioscler Thromb Vasc Biol  2016;27:321
  9. Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5'-Monophosphate-Activated Protein Kinase.
    Authors: M?ller-Durovic Et al.
    J Immunol  2016;197:2891
  10. Activation of AMPK-induced autophagy ameliorates Huntington disease pathology in vitro.
    Authors: Walter Et al.
    Neuropharmacology  2016;108:24
  11. Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids.
    Authors: Peart Et al.
    Oncotarget  2015;6:22424
  12. Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury.
    Authors: Hwang Et al.
    J Pharmacol Exp Ther  2015;38:843
  13. Dynamics of elongation factor 2 kinase regulation in cortical neurons in response to synaptic activity.
    Authors: Kenney Et al.
    J Neurosci  2015;35:3034
  14. Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells.
    Authors: Weikel Et al.
    Am J Physiol Cell Physiol  2015;308:C249
  15. A novel MEK-ERK-AMPK signaling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells.
    Authors: López-Cotarelo Et al.
    Mol Cell  2015;290:827
  16. Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway.
    Authors: Mo Et al.
    Nat Cell Biol  2015;17:500
  17. Bidirectional regulation of P body formation mediated by eIF4F complex formation in sensory neurons.
    Authors: Melemedjian Et al.
    Neurosci Lett  2014;563:169
  18. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1.
    Authors: Wu Et al.
    Arthritis Rheum  2013;49:1167
  19. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization.
    Authors: Mack Et al.
    Autophagy  2012;8:1197
  20. Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways.
    Authors: Lo Et al.
    J Cell Biol  2012;199:1117
  21. Chondrocyte AMP-activated protein kinase activity suppresses matrix degradation responses to proinflammatory cytokines interleukin-1β and tumor necrosis factor α.
    Authors: Terkeltaub Et al.
    Proc Natl Acad Sci U S A  2011;63:1928
  22. 5-Aminoimidazole-4-carboxyamide-ribonucleoside (AICAR)-stimulated hepatic expression of Cyp4a10, Cyp4a14, Cyp4a31, and other peroxisome proliferator-activated receptor α-responsive mouse genes is AICAR 5'-monophosphate-dependent and AMP-activated
    Authors: Bumpus and Johnson
    J Biol Chem  2011;339:886
  23. AMP-activated protein kinase suppresses endothelial cell inflammation through phosphorylation of transcriptional coactivator p300.
    Authors: Zhang Et al.
    Mol Cells  2011;31:2897
  24. Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury.
    Authors: Paiva Et al.
    Am J Physiol Heart Circ Physiol  2011;300:H2123


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