AICAR is an adenosine analog that is phosphorylated in whole cells to form 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5′-monophosphate (ZMP), which stimulates AMPK activity1. AICAR acts by entering nucleoside pools, significantly increasing levels of adenosine during periods of ATP breakdown. AICAR mimics the effects of insulin on the expression of two gluconeogenic genes PEPCK and glucose-6-phosphatase2. AICAR inhibits PPARα coactivation3 and adipocyte differentiation4. AICAR is a substrate for the AICAR transformylase activity of ATIC5. AICAR is also known as 5-amino-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide, N1-(β-D-Ribofuranosyl)-5-aminoimidazole-4-carboxamide, and Acadesine.

AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a substance produced naturally by the body that stimulates AMP activated protein kinase (AMPK), a protein that regulates metabolism in a variety of ways. AMPK acts as an energy regulator and is activated during exercise or other circumstances that use up cellular energy.

The AMPK-stimulating AICAR can also be synthesized in a lab and is being evaluated in preclinical research and human clinical trials as a therapeutic agent to treat certain metabolic disorders in humans.

Biological Activity

AICAR, also known as acadesine, is an adenosine regulating agent and AMPK activator. AICAR was found to activate AMP-activated protein kinase (AMPK) in skeletal muscle, inhibit acetyl-CoA carboxylase, reduce malonyl-CoA, and increase fatty acid oxidation and glucose uptake. 

Augments proliferation, differentiation and mineralization of osteoblastic MC3T3-EI cells and attenuates psychosine-induced expression of proinflammatory cytokines and iNOS in astrocytes. Promotes osteogenic differentiation of hAMSCs and BM-MSCs in vitro.