AICAR

Product Details

AICAR (Acadesine, AICA-riboside) — Research Grade AMPK Activator, ≥98% Purity (HPLC)

Nucleoside analog. AMPK activator via ZMP. Exercise mimetic research tool. Powder. Lot-specific COA included.

AICAR peptide  (5-aminoimidazole-4-carboxamide ribonucleoside), also known as acadesine or AICA-riboside, is a nucleoside analog and cell-permeable activator of AMP-activated protein kinase (AMPK). It is not a peptide. The compound was originally developed not for metabolic research but for cardioprotection during coronary artery bypass graft (CABG) surgery, where adenosine regulation was hypothesized to reduce ischemic injury. That clinical program, conducted in the 1990s, found cardiovascular benefits in some populations but failed to meet primary endpoints broadly enough to secure FDA approval.

The mechanism is well characterized. AICAR enters cells via adenosine transporters and is phosphorylated by intracellular adenosine kinase to form ZMP (5-aminoimidazole-4-carboxamide ribonucleotide), an AMP analog. ZMP binds AMPK at the same sites as AMP and mimics all of the effects of AMP on the AMPK system. Because ZMP can accumulate to millimolar concentrations in cells, AICAR directly activates AMPK in most cell types.

The landmark 2008 Narkar Cell study established AICAR’s research profile. In sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. That finding triggered widespread media coverage of “exercise in a pill” and prompted WADA to prohibit AICAR in 2009.

Supplied as a research-grade powder for in vitro and preclinical research applications. Each lot is independently verified for purity and identity and ships with a Certificate of Analysis.

Specifications

Note: AICAR is a nucleoside analog, not a peptide. Solubility varies by supplier and method; some suppliers report water solubility as high as 52.9 mg/mL. For obtaining higher solubility, warm the tube at 37 °C and shake in an ultrasonic bath. Verify the exact purity, appearance, and solubility against the Certificate of Analysis supplied with your lot.

Research applications

AICAR is used in laboratory settings to investigate:

• AMPK signaling and energy homeostasis — activation of AMPK via ZMP accumulation, and downstream phosphorylation of acetyl-CoA carboxylase (ACC) in skeletal muscle and hepatocyte models

• Glucose uptake and GLUT4 translocation — acute and chronic AICAR treatment increases skeletal muscle glucose uptake and GLUT-4 protein content, with AMPK activation totally enhancing glucose metabolism

• Fatty acid oxidation — hindlimbs perfused with 2 mM AICAR for 45 minutes exhibited a 2.8-fold increase in fatty acid oxidation

• Exercise mimetic research — the 2008 Narkar Cell study demonstrating 44% endurance enhancement in sedentary mice, and subsequent work on the AMPK–PPARδ pathway

• Mitochondrial biogenesis — AICAR’s effects on mitochondrial function and the SIRT1 pathway, with short-term treatment enhancing AMPK and ACC phosphorylation and increasing SIRT1 protein expression

• Cardioprotection research — the original CABG clinical program context, where adenosine regulation was hypothesized to reduce ischemic injury

• Lesch-Nyhan disease research — a Phase II pilot study (NCT00004314) examining AICAR’s effects on hematologic manifestations, behavioral and neurological symptoms, and purine production in men with Lesch-Nyhan syndrome

• Type 2 diabetes research — a clinical study (NCT00168519) assessing AICAR’s impact on whole-body glucose and fatty acid metabolism in type 2 diabetic patients

• Anti-doping detection research — development of GC/C/IRMS methods for distinguishing endogenous and exogenous AICAR in urine, with a detection window of approximately 16 hours after a low 3-gram dose

• Analytical method development — HPLC and NMR quantification and reference standard preparation for nucleoside analog analysis

Handling and storage

Store the powder at −20 °C, desiccated and protected from light. Powder is stable for up to 3 years at −20 °C or 2 years at 4 °C. AICAR is soluble in water at approximately 20 mg/mL with warming and in DMSO at approximately 40 mg/mL. Prepare stock solutions under aseptic conditions. Aliquot stock solutions to avoid repeated freeze-thaw cycles. Store solutions at −20 °C, protected from light, and use within 12 months to prevent loss of potency.

For laboratory use by qualified personnel only.