Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases

J Med Chem. 2015 Jan 8;58(1):2-29. doi: 10.1021/jm401994c. Epub 2014 Aug 28.


Adenosine 5'-monophosphate activated protein kinase (AMPK) is a master sensor of cellular energy status that plays a key role in the regulation of whole-body energy homeostasis. AMPK is a serine/threonine kinase that is activated by upstream kinases LKB1, CaMKKβ, and Tak1, among others. AMPK exists as αβγ trimeric complexes that are allosterically regulated by AMP, ADP, and ATP. Dysregulation of AMPK has been implicated in a number of metabolic diseases including type 2 diabetes mellitus and obesity. Recent studies have associated roles of AMPK with the development of cancer and neurological disorders, making it a potential therapeutic target to treat human diseases. This review focuses on the structure and function of AMPK, its role in human diseases, and its direct substrates and provides a brief synopsis of key AMPK modulators and their relevance in human diseases.

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*
  • Adenine Nucleotides / chemistry
  • Adenine Nucleotides / metabolism*
  • Adenine Nucleotides / pharmacology
  • Allosteric Regulation / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / pharmacology
  • Metabolic Diseases / drug therapy
  • Molecular Structure
  • Neoplasms / drug therapy
  • Protein Structure, Tertiary
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*


  • Adenine Nucleotides
  • Intracellular Signaling Peptides and Proteins
  • Small Molecule Libraries
  • protein kinase modulator
  • AMP-Activated Protein Kinases