AICAR
A cell-permeable nucleoside analog used to activate AMPK and probe metabolic stress signaling in experimental systems.
What AICAR is
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside; also called acadesine) is a cell-permeable precursor that is phosphorylated inside cells to ZMP, an AMP mimetic. It is one of the classic pharmacological tools for activating AMP-activated protein kinase (AMPK) in metabolic, exercise-physiology, and cancer-biology experiments.
Researchers adopted AICAR because AMPK sits at a central energy-sensing node controlling fatty-acid oxidation, glucose uptake, mitochondrial biogenesis programs, and cell-growth checkpoints. At the same time, the literature candidly documents AMPK-independent effects and dose-dependent toxicity signals, including nucleotide-pool disruption and antiproliferative stress. Those safety and off-target findings are part of the scientific record and matter for experimental design.
Research-grade AICAR is Research Use Only. It is not an approved exercise drug or metabolic therapeutic in this RUO context and is not for human consumption. Ranges below are experimental-reference values only.
How it works
After cellular uptake, AICAR is converted to AICAR monophosphate (ZMP). ZMP mimics rising AMP and promotes AMPK activation through the canonical energy-sensing mechanism. Activated AMPK phosphorylates downstream metabolic targets that generally favor catabolic ATP-generating pathways and restrain anabolic processes. Importantly, ZMP also perturbs purine/pyrimidine nucleotide homeostasis at higher exposures, which can drive antiproliferative and cytotoxic effects independent of simple AMPK activation.
The research context
Metabolic biochemists, muscle physiologists, and cancer-metabolism labs are the heaviest users. AICAR remains a reference AMPK probe even as more selective activators have emerged, partly because decades of comparative data already exist.
What the research examines
Research areas, not results. A topic on this list is being studied, not settled.
How it appears in the literature
How these amounts appear in the literature. Read the study before reading the number.
| Research context | Reported amount | Frequency | Route |
|---|---|---|---|
| Common rodent in vivo research exposures reported across metabolic studies | 250 mg – 500 mg | often once daily in short preclinical protocols | intraperitoneal (preclinical) |
| In vitro culture concentrations commonly cited | 100 mcg – 2 mg | continuous media exposure for hours to days | cell culture media |
Handling & storage
Store solid AICAR dry and cold per supplier specifications. Solutions should be prepared fresh or aliquoted and protected from repeated freeze-thaw according to lab SOP, because nucleoside solutions can degrade.
Notes on combined research
Experimental papers often compare AICAR with exercise, metformin, or newer AMPK activators rather than stacking it as a peptide companion. In metabolic research it may appear alongside endurance-training protocols or glucose-uptake assays. Designers should control for nucleotide-metabolism confounds when interpreting AMPK-specific claims.
AICAR questions
Rodent metabolic studies frequently use about 250-500 mg/kg, while cell-culture work uses micromolar to millimolar media concentrations. Human performance use is not an approved or appropriate RUO framing.
No. AICAR is a nucleoside analog / AMPK-activating small molecule, not a peptide. It appears on peptide-education sites because adjacent research communities study it with metabolic peptides.
Peer-reviewed work reports dose-dependent disruption of nucleotide homeostasis, antiproliferative stress, and context-specific cytotoxicity. These findings are a standard part of responsible AICAR experimental design.
No. While it is a classic AMPK activator, literature shows AMPK-independent metabolic and nucleotide-pool effects, especially at higher concentrations.
RUO AICAR is laboratory material, not a dietary supplement or approved sports drug, and is not for human consumption.
Because AMPK activation and nucleotide-pool stress can suppress proliferation in some tumor-cell models, making AICAR a mechanistic probe in cancer metabolism.
Prepare to known molarity, verify solubility, protect from unnecessary freeze-thaw, and include vehicle controls. Concentration-response curves help separate AMPK effects from toxicity.
Read the research yourself
These references were validated against the NCBI database. No citation appears here unless it resolves to a real paper.
- Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR).PubMed
- Metabolomics and proteomics identify the toxic form and the associated cellular binding targets of the anti-proliferative drug AICAR.PubMed
- AICAr suppresses cell proliferation by inducing NTP and dNTP pool imbalances in acute lymphoblastic leukemia cells.PubMed
- AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.PubMed
- AMP-activated protein kinase activator AICAR acutely lowers blood pressure and relaxes isolated resistance arteries of hypertensive rats.PubMed