AICAR

Overview

AICAR — acadesine, or AICA riboside — is not a peptide but a purine nucleoside analogue, and it is included in this database because it appears in the same metabolic research literature as several of the peptides above. Once taken up by the cell it is phosphorylated to ZMP, a molecule that mimics AMP closely enough to activate AMP-activated protein kinase (AMPK) allosterically. AMPK is the central cellular energy sensor, and because AICAR activates it without the cell actually being energy-depleted, it has become a standard experimental tool for asking what AMPK activation does in isolation. The published literature is substantial and spans skeletal muscle glucose uptake, insulin sensitivity, mitochondrial biogenesis, cardioprotection, and cognition in rodent models. It is also a prohibited substance in sport, and part of the indexed literature concerns its detection in doping control. Unlike most compounds in this database, the evidence base here is broad and comes from many independent laboratories.

For research use only · Not FDA/EMA approved · Not for human consumption

Mechanism of Action

Published research describes AICAR entering cells through adenosine transporters and being phosphorylated by adenosine kinase to ZMP (AICAR monophosphate). ZMP binds the γ-subunit of AMPK at the sites normally occupied by AMP, producing allosteric activation and promoting phosphorylation of Thr172 on the α-subunit by upstream kinases including LKB1. Nakano and colleagues reported that this activation is isoform-selective, favouring the α2 complex. Downstream, published studies describe increased GLUT4 translocation and glucose uptake in skeletal muscle independent of insulin, increased fatty acid oxidation through inhibition of acetyl-CoA carboxylase, and transcriptional effects on mitochondrial biogenesis. Cantó and colleagues reported that AMPK activation modulates NAD+ metabolism and SIRT1 activity, linking the pathway to the sirtuin literature. Kjøbsted and colleagues have reported that prior AICAR stimulation increases subsequent insulin sensitivity in an AMPK-dependent manner requiring TBC1D4. Dolinar and colleagues reported an important experimental caveat: nucleosides present in culture media can block AICAR-stimulated AMPK activation, which matters for interpreting in vitro work.

For research use only · Not FDA/EMA approved · Not for human consumption

Key Research Areas

• AMPK activation and isoform selectivity in skeletal muscle
• Insulin-independent glucose uptake and GLUT4 expression
• Prior-stimulation effects on subsequent insulin sensitivity (TBC1D4-dependent)
• Fatty acid oxidation and mitochondrial biogenesis
• NAD+ metabolism and SIRT1 crosstalk
• Cardioprotection in ischaemia models
• Cognition and motor coordination in young and aged mice
• Detection and metabolism in doping control samples

For research use only · Not FDA/EMA approved · Not for human consumption

Published Studies (8 cited)

For research use only · Not FDA/EMA approved · Not for human consumption

Dosage in Published Research

Published rodent protocols commonly use 250–500 mg/kg/day by intraperitoneal or subcutaneous injection, with chronic studies running from days to several weeks. In vitro work typically uses 0.5–2 mM in culture medium, and the Dolinar work above is a reminder that medium composition materially affects the response at those concentrations. Protocols vary widely by tissue and model, and no standardised research protocol exists. All figures are cited from published literature for reference only.

For research use only · Not FDA/EMA approved · Not for human consumption

Storage & Handling

Store lyophilized powder at -20°C for long-term storage, protected from light and moisture. Solutions in aqueous buffer should be prepared fresh where possible; if stored, keep at 2–8°C and use within 14 days. Avoid repeated freeze-thaw cycles. Handle under sterile laboratory conditions using appropriate PPE.

For research use only · Not FDA/EMA approved · Not for human consumption

Safety Profile (Literature Only)

Acadesine has been studied in human clinical trials in cardiac surgery and in haematological indications under its pharmaceutical name, so more human exposure data exists for this compound than for most in this database — but that data belongs to specific clinical contexts and does not transfer to research use. Published rodent studies describe tolerance of chronic dosing at the levels above. AICAR is on the WADA prohibited list, and part of the published literature concerns its detection in competition samples. This compound is for laboratory research use only.

For research use only · Not FDA/EMA approved · Not for human consumption