AMP-activated protein kinase: the current landscape for drug development

Nat Rev Drug Discov. 2019 Jul;18(7):527-551. doi: 10.1038/s41573-019-0019-2.


Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elicit beneficial effects has been challenging. However, in recent years, direct AMPK activators have been identified and tested in preclinical models, and a small number have entered clinical trials. Despite these advances, which disease(s) represent the best indications for therapeutic AMPK activation and the long-term safety of such approaches remain to be established.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Binding Sites
  • Carbohydrate Metabolism / drug effects*
  • Drug Development / methods*
  • Energy Metabolism / drug effects*
  • Humans
  • Lipid Metabolism / drug effects*
  • Protein Binding
  • Protein Conformation
  • Protein Isoforms
  • Signal Transduction
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use


  • Protein Isoforms
  • Small Molecule Libraries
  • AMP-Activated Protein Kinases