AICAR

AICAR (5-Aminoimidazole-4-carboxamide Ribonucleotide)

AICAR, also known as 5-aminoimidazole-4-carboxamide ribonucleotide or Acadesine, is an adenosine monophosphate (AMP) analog that activates AMP-activated protein kinase (AMPK). AMPK serves as a central energy sensor regulating glucose uptake, lipid oxidation, and mitochondrial biogenesis. AICAR is widely used in biochemical and metabolic research to study energy metabolism, exercise physiology, and cellular stress responses.

Overview

AICAR is phosphorylated intracellularly to form ZMP (AICA ribotide), which mimics AMP and directly activates AMPK. This activation promotes catabolic pathways that generate ATP while suppressing anabolic processes that consume energy.
Through AMPK activation, AICAR enhances fatty acid oxidation, glucose transport, and mitochondrial enzyme expression, providing a pharmacological model for exercise-mimetic and metabolic regulation studies. It has been investigated for its potential effects in diabetes, ischemia, cardiac metabolism, and muscle endurance models.

Chemical Makeup

• Chemical Name: 5-Aminoimidazole-4-carboxamide ribonucleotide
• Molecular Formula: C9H15N4O8P
• Molecular Weight: 338.22 g/mol
• CAS Number: 2627-69-2
• Compound Class: AMP analog; AMPK activator
• Purity: ≥99% (per COA)
• Form: Lyophilized powder
• Sizes Available: 50 mg, 100 mg, 500 mg vials
  
  

Research and Clinical Studies

AMPK Activation and Energy Metabolism
AICAR acts as a direct activator of AMPK, stimulating energy-conserving pathways that enhance glucose uptake and lipid oxidation. Research models have shown increased glucose transport in skeletal muscle and improved insulin sensitivity.

Exercise and Endurance Models
In murine studies, AICAR administration has mimicked key effects of endurance exercise, including mitochondrial biogenesis, oxidative metabolism, and improved physical performance without actual exercise training.

Cardiac Metabolism and Ischemia
AICAR has demonstrated cardioprotective effects in ischemic models by enhancing ATP regeneration and maintaining cellular energy balance through AMPK activation.

Metabolic Disorders and Insulin Sensitivity
Preclinical research shows AICAR improves insulin sensitivity, reduces hepatic lipid accumulation, and promotes glucose utilization in metabolic syndrome and type 2 diabetes models.

Mitochondrial and Cellular Stress Research
AICAR induces PGC-1α expression and mitochondrial DNA replication, making it a key compound in mitochondrial biogenesis studies and in cellular models of oxidative stress and aging.

Pharmacokinetics
AICAR is cell-permeable and rapidly phosphorylated intracellularly to ZMP, which accumulates and activates AMPK-dependent pathways for several hours post-exposure in vitro and in vivo.

AICAR is available for research and laboratory purposes only. Not for human consumption.

References

1. Corton JM, et al. Activation of AMP-activated protein kinase by AICAR: mechanism and effects on metabolic regulation. Eur J Biochem. 1995;229(2):558–565. https://pubmed.ncbi.nlm.nih.gov/7744031/
   
2. Hardie DG. AMPK: a key regulator of energy balance. Nat Rev Mol Cell Biol. 2015;16(12):727–741. https://pubmed.ncbi.nlm.nih.gov/26549594/
   
3. Merrill GF, et al. AICAR stimulates glucose transport and metabolism by activation of AMPK. Am J Physiol. 1997;273(6):E1107–E1112. https://pubmed.ncbi.nlm.nih.gov/9435525/
   
4. Winder WW, et al. AICAR treatment increases fatty acid oxidation in skeletal muscle. Am J Physiol. 2000;279(5):E1106–E1112. https://pubmed.ncbi.nlm.nih.gov/11052966/
   
5. Narkar VA, et al. AMPK and PPARδ agonists mimic exercise by reprogramming muscle metabolism. Cell. 2008;134(3):405–415. https://pubmed.ncbi.nlm.nih.gov/18674809/
   
6. Cool B, et al. Identification and characterization of a small molecule AMPK activator. Cell Metab. 2006;3(6):403–416. https://pubmed.ncbi.nlm.nih.gov/16753576/
   
7. Russell RR 3rd, et al. AMPK activation protects the heart during ischemia. Am J Physiol. 2004;287(6):H2552–H2558. https://pubmed.ncbi.nlm.nih.gov/15284074/
   
8. Steinberg GR, Kemp BE. AMPK in health and disease. Physiol Rev. 2009;89(3):1025–1078. https://pubmed.ncbi.nlm.nih.gov/19584320/
   
9. Canto C, Auwerx J. PGC-1α, SIRT1 and AMPK in energy metabolism. Cell Metab. 2009;9(5):385–391. https://pubmed.ncbi.nlm.nih.gov/19356710/
   
10. Guigas B, et al. AMPK activation by AICAR regulates lipid metabolism and glucose homeostasis. Biochem Pharmacol. 2006;71(12):1689–1699. https://pubmed.ncbi.nlm.nih.gov/16650814/