Product details
AICAR (5-Aminoimidazole-4-carboxamide riboside / AICA-riboside), also known as Acadesine, is the nucleoside form of this purine analog; intracellularly it is phosphorylated to ZMP (the corresponding ribonucleotide), which mimics AMP and activates AMP-activated protein kinase (AMPK), the master energy-sensor kinase that responds to cellular ATP depletion. AICAR has been studied since the 1990s in energy-metabolism, muscle-physiology, and exercise-mimetic research; it was one of the first compounds to be discussed as a potential pharmacological mimic of endurance training because chronic AMPK activation produces gene-expression changes similar to those induced by endurance exercise. The molecule reached Phase 3 clinical development for several cardioprotection indications but did not achieve regulatory approval; it remains widely used as a research tool for AMPK pathway studies.
Peptuno supplies AICAR as the free base at ≥99.0% HPLC purity. As a small molecule, the analytical workflow uses RP-HPLC plus UV-Vis identity. Two large fill sizes (50 mg and 100 mg) match the dosing scales typical for cell-culture and in vivo AMPK-activation studies, which often require higher absolute amounts than peptide research.
FAQ
- How does AICAR activate AMPK, and why is that mechanistically interesting?
- AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) is converted intracellularly to ZMP, a metabolic mimic of AMP. ZMP binds to AMPK's regulatory γ-subunit at the same site that AMP normally engages, allosterically activating the kinase as if cellular AMP/ATP ratio were elevated, without requiring actual ATP depletion. AMPK activation triggers the canonical energy-stress response: enhanced fatty-acid oxidation, glucose uptake, mitochondrial biogenesis, and autophagy, while suppressing energy-consuming anabolic processes. AICAR is therefore the standard pharmacological tool for studying AMPK biology in isolation from the actual ATP depletion that would activate AMPK physiologically.
- Why didn't AICAR achieve regulatory approval despite Phase 3 development?
- AICAR (under the development name Acadesine) advanced through Phase 3 clinical trials for cardioprotection in coronary artery bypass graft surgery in the late 1990s and early 2000s. The trials produced mixed efficacy signals and the program was discontinued. The molecule has since been widely used as a research tool for AMPK pathway studies but is not approved as a finished drug in any jurisdiction. AICAR also has a complicated history with anti-doping enforcement, it has been on WADA's prohibited list since 2009 as a 'metabolic modulator', which is the basis for the molecule's regulated status in athletic contexts.
- What's the recommended dosing range for AICAR in cellular and in vivo research models?
- Cellular AMPK-activation studies typically use AICAR at 0.1-2 mM working concentrations, high relative to most pharmacological compounds because AICAR must be transported into cells and converted to ZMP by adenosine kinase before it can engage AMPK. The high in vitro concentration is the reason AICAR is supplied in 50-100 mg fill sizes rather than the μg-mg scales typical of peptide research. For in vivo rodent studies, published protocols use AICAR at 250-500 mg/kg IP, daily for 1-4 weeks; the IP route bypasses the first-pass conversion limitations of oral dosing. Buyers should reference the specific protocol being replicated for dose selection rather than treating AICAR dose-response as universal across systems.
- What's the difference between AICAR and other AMPK activators (metformin, A-769662, MK-8722)?
- AICAR is the original AMP-mimetic AMPK activator and remains the most-cited research tool, but the AMPK-activator toolkit has expanded considerably since its discovery. Metformin activates AMPK indirectly through complex I inhibition and mitochondrial AMP/ATP-ratio changes, different mechanism, broader off-target profile. A-769662 is an allosteric AMPK activator that binds at a distinct site from the AMP/ZMP-binding pocket; useful for distinguishing AMP-mimetic from non-AMP-mimetic AMPK biology. MK-8722 is a newer pan-isoform AMPK activator with higher potency than A-769662. The choice of AMPK activator depends on the experimental question: AICAR for canonical AMP-mimetic biology, A-769662 or MK-8722 for AMP-independent AMPK pharmacology, metformin for translationally relevant mechanism studies.
Certificate of Analysis (COA)
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