Targeting AMPK: From Ancient Drugs to New Small-Molecule Activators

  • Bruno GuigasEmail author
  • Benoit Viollet
Part of the Experientia Supplementum book series (EXS, volume 107)


The AMP-activated protein kinase (AMPK) is an evolutionary conserved and ubiquitously expressed serine/threonine kinase mainly acting as a key regulator of cellular energy homeostasis. AMPK is a heterotrimeric protein complex, consisting of a catalytic α subunit and two regulatory β and γ subunits, whose activity is tightly regulated by changes in adenine nucleotides and several posttranslational modifications. Once activated in response to energy deficit, AMPK concomitantly inhibits ATP-consuming anabolic processes and promotes ATP-generating catabolic pathways via direct phosphorylation of multiple downstream effectors, leading to restoration of cellular energy balance. A growing number of energy/nutrient-independent functions of AMPK are also regularly reported, progressively expanding its role to regulation of non-metabolic cellular processes. Historically, AMPK as a therapeutic target has attracted much of interest due to its potential impact on metabolic disorders, such as obesity and type 2 diabetes, but has also recently received considerable renewed attention in the framework of cancer studies, highlighting the persistent need for selective, reversible, potent, and tissue-specific activators. In this chapter, we review the most recent advances in the understanding of the mechanism(s) of action of the current portfolio of AMPK activators, including plant-derived natural compounds and newly discovered small-molecule agonists directly targeting various AMPK subunits.


AMPK Metformin Salicylate A-769662 Compound-13 991 


Duality of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of ParasitologyLeiden University Medical CenterLeidenThe Netherlands
  3. 3.INSERM, U1016, Institut CochinParisFrance
  4. 4.CNRS, UMR8104ParisFrance
  5. 5.Université Paris DescartesSorbonne Paris CitéFrance

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