AICAR
AMPK activator (small molecule)
An AMP-activated protein kinase (AMPK) activator studied in exercise-mimetic and energy-metabolism research.
Also referenced as: Acadesine, 5-Aminoimidazole-4-carboxamide riboside
Overview
AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide, also called acadesine) is a small-molecule nucleoside analog and an intermediate in de novo purine biosynthesis. It is not a peptide.
At a glance
What AICAR does
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside, also called acadesine) is a nucleoside rather than a peptide, and its metabolic action is one of the most directly mechanistic in this group. Once inside the cell it is phosphorylated to its monophosphate form, ZMP, which structurally mimics AMP. Because AMP is the signal a cell reads as 'low energy,' ZMP allosterically activates AMPK, the master energy-sensing kinase, by binding its gamma subunit, effectively tricking the cell into an energy-deficit state without actually depleting ATP. Activated AMPK then triggers a broad catabolic program: it phosphorylates and inhibits acetyl-CoA carboxylase (ACC), lowering malonyl-CoA and releasing the brake on fatty-acid oxidation; it drives GLUT4 translocation to increase insulin-independent glucose uptake; it upregulates PGC-1alpha to promote mitochondrial biogenesis; and it inhibits mTOR, favoring autophagy over growth.
The landmark preclinical result is that sedentary mice given AICAR for four weeks, with no exercise, showed roughly a 44% increase in treadmill running endurance, a shift toward oxidative type-I muscle fibers, higher mitochondrial density, and upregulation of a cluster of oxidative-metabolism genes, adaptations that normally take weeks of endurance training. This is why AICAR is often called the original exercise mimetic. It also has a history in cardiac ischemia research. The efficacy evidence for metabolic/endurance effects is animal and cell-based; there is no established human weight-loss indication, and notably AICAR is on the WADA prohibited list as a metabolic modulator in sport.
Effects reported in research
- Phosphorylated intracellularly to ZMP, an AMP mimetic that allosterically activates AMPK (core mechanism).
- Inhibits acetyl-CoA carboxylase (ACC), lowering malonyl-CoA and enhancing fatty-acid oxidation.
- Promotes GLUT4 translocation, increasing insulin-independent glucose uptake into muscle.
- Upregulates PGC-1alpha and drives mitochondrial biogenesis (animal/cell data).
- Increased treadmill running endurance ~44% in sedentary, untrained mice over four weeks.
- Shifted muscle toward oxidative type-I fibers with increased mitochondrial density in mice.
- Upregulated a set of ~32 oxidative-metabolism genes in mouse muscle (exercise-like signature).
- Inhibits mTOR, favoring autophagy — a mechanistic effect studied in cells. No established human weight-loss indication; banned by WADA in sport.
Effects listed reflect findings reported in the research literature — many in animal or in-vitro models. Listing an effect is not a claim of efficacy or a therapeutic indication in humans.
Mechanism of action
Inside cells AICAR is phosphorylated to ZMP, an AMP analog that activates AMP-activated protein kinase (AMPK), a central sensor of cellular energy status. AMPK activation shifts metabolism toward catabolic, energy-generating pathways, including increased glucose uptake and fatty-acid oxidation. In preclinical studies AICAR has been used as a pharmacological AMPK activator and described as an exercise-mimetic.
Mechanistic description reflects published research-literature understanding. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
What it's studied for
Research contexts in which AICAR appears in the literature. Listing a research area is not a claim of efficacy or a therapeutic indication.
Key characteristics
- A small-molecule nucleoside analog, NOT a peptide
- Activates AMPK via its phosphorylated form (ZMP), an AMP mimic
- Widely used as a research tool to study AMPK-dependent metabolism
- Investigated clinically as acadesine in other contexts (e.g., cardiac surgery)
- A prohibited substance in sport (WADA) as a metabolic modulator
Reported research dosing reference only
Educational reference, not dosing guidance. The figures below summarize amounts reported in published research and research-community protocols, provided for educational and research context only. They are not medical advice, not a recommendation, and not instructions for human use. AICAR is a research compound.
Reported research dosing comes from cell-culture and rodent studies rather than established human protocols. Published in-vivo work uses body-weight-scaled intraperitoneal dosing. These are figures reported for research context only, not dosing guidance for humans.
- Rodent studies: reported at ~250-500 mg/kg administered intraperitoneally, often daily
- High-dose muscle-physiology research: up to ~1 g/kg reported in some studies
- In vitro: ~0.5-2 mM in culture medium
Small-molecule nucleoside (parent plasma half-life ~90 min; intracellular ZMP sustains AMPK activation for hours). Human dosing not established; research reference only.
How it compares
Unlike SLU-PP-332 (ERR-level) or the GH fragments, AICAR acts directly on the AMPK energy-sensing pathway as an AMP analog.
Commonly studied alongside
Compounds frequently researched together with AICAR in the literature. Cross-referenced for research context — not a usage or combination recommendation.
Compare and calculate
Side-by-side pages for the pairings the literature already documents for AICAR, plus the unit-conversion reference for a reconstituted vial. Factual comparisons of documented characteristics — not a recommendation to combine or use any compound.
Handling & Stability
Storage and handling depend on the supplied form, which varies for this compound. Follow the supplier’s stated conditions and shelf life.
- Avoid repeated freeze-thaw cycles
- Verify supplier lot and Certificate of Analysis
- Follow institutional lab-safety protocols
Analytical & COA Concepts
Reputable research suppliers publish a third-party Certificate of Analysis per batch. Key analytical concepts referenced in COAs include:
Category Context
AICAR sits in the Metabolic & Mitochondrial area of the PeptiDex library.
- Entry type: Research compound reference
- Metabolic & Mitochondrial category hub →
- Browse the full library →
- Glossary of terms →
Where researchers source AICAR
For researchers studying AICAR, third-party suppliers such as Practically Natty Peptides offer research-grade material, third-party tests every batch and provides Certificates of Analysis on request, and ship from the US.
PeptiDex does not maintain a direct supplier listing for this compound. The link above goes to a third-party research-supplier directory.
Frequently asked questions
Is AICAR a peptide?
No. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, also called acadesine or AICA-riboside) is a small-molecule nucleoside, not a peptide. Its molecular formula is C9H14N4O5 (MW ~258.2, CAS 2627-69-2) and it has no amino-acid sequence.
What is the mechanism of AICAR?
Inside cells AICAR is phosphorylated to ZMP, an AMP mimetic that activates AMP-activated protein kinase (AMPK). AMPK activation shifts metabolism toward energy production, increasing glucose uptake and fatty-acid oxidation. Because AMPK is a key exercise-responsive energy sensor, AICAR is studied as an exercise-mimetic metabolic compound.
What is AICAR studied for?
AICAR is a widely-used research tool for AMPK biology and is studied in models of glucose metabolism, endurance/muscle physiology, mitophagy, and metabolic disease. It has also been examined in cardioprotection (acadesine). Its exercise-mimetic effects on endurance in rodents led to attention from anti-doping authorities.
What does AICAR's half-life imply for research design?
The plasma half-life of the parent riboside is on the order of ~90 minutes, but the intracellular ZMP metabolite persists longer, sustaining AMPK activation for several hours after a bolus. This is why in-vivo protocols often use daily bolus dosing while accepting that the pharmacodynamic effect outlasts plasma clearance.
How is AICAR used in vitro versus in vivo?
In cell-culture work AICAR is typically applied at ~0.5-2 mM in medium to activate AMPK, while in rodent studies it is commonly given by intraperitoneal injection at higher body-weight-scaled doses. As a small-molecule nucleoside it is comparatively stable and does not require lyophilized-peptide handling.
Answers are educational summaries of research-literature context and do not constitute medical advice. See the Research Library, COA guide, and Storage & Handling guide for more.
References
Primary literature indexed in PubMed for AICAR. Listing a study records that it exists and is indexed — it is not a claim of efficacy, a therapeutic indication, or an endorsement of its conclusions. Much of this literature is preclinical (in-vitro or animal-model).
- AMPK and PPARdelta agonists are exercise mimetics
- Combined pharmacological activation of AMPK and PPARδ potentiates the effects of exercise in trained mice
Each reference was checked against its PubMed record on 2026-07-28: the PMID resolves and the title, journal and year match. Where no indexed literature exists for a compound, PeptiDex says so rather than substituting a citation about a different molecule. See the editorial policy.