AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review

Cells. 2021 May 4;10(5):1095. doi: 10.3390/cells10051095.


5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology. However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway.

Keywords: AICAr; AMPK; acadesine; cancer; cell cycle; exercise; leukemia; metabolism; purine; pyrimidine.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Carcinogenesis / drug effects
  • Cell Cycle / drug effects
  • Energy Metabolism / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Myocytes, Cardiac / drug effects
  • Protein Kinases / metabolism*
  • Ribonucleotides / pharmacology*


  • Hypoglycemic Agents
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • AICA ribonucleotide