AICAR¶
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide, CAS 2627-69-2) is a cell-permeable adenosine analog and precursor of ZMP (5-aminoimidazole-4-carboxamide ribonucleotide monophosphate), with a molecular weight of approximately 258.2 Da and formula C₉H₁₄N₄O₅. Upon intracellular phosphorylation to ZMP, AICAR functions as a pharmacological activator of AMP-activated protein kinase (AMPK), the master cellular energy sensor. It is a critical research tool in metabolic biology, exercise physiology, and energy homeostasis signaling.
Technical Specifications¶
| Property | Value |
|---|---|
| CAS Number | 2627-69-2 |
| Molecular Formula | C₉H₁₄N₄O₅ |
| Molecular Weight | ~258.2 Da |
| Purity | ≥98% (HPLC-verified) |
| Appearance | Lyophilized white powder |
| Solubility | Soluble in sterile water and aqueous buffers |
| Storage | -20°C (lyophilized), 2–8°C (reconstituted) |
Mechanism of Action¶
AICAR is taken up by cells via adenosine transporters and phosphorylated by adenosine kinase to form ZMP (AICAR monophosphate), which mimics the effects of AMP (adenosine monophosphate) on AMPK. ZMP binds to the γ-regulatory subunit of AMPK, inducing an allosteric conformational change that: (1) promotes phosphorylation of Thr¹⁷² in the α-catalytic subunit activation loop by upstream kinases LKB1 and CaMKKβ, (2) inhibits dephosphorylation of this site by protein phosphatases (PP2A/PP2C), and (3) allosterically activates the phosphorylated enzyme by ~10-fold. Activated AMPK then phosphorylates downstream targets to shift cellular metabolism from anabolic (ATP-consuming) to catabolic (ATP-generating) states: it phosphorylates and inactivates acetyl-CoA carboxylase (ACC), reducing malonyl-CoA levels and disinhibiting mitochondrial fatty acid uptake via CPT-1; it activates glucose transporter GLUT4 translocation to increase glucose uptake independently of insulin; and it promotes mitochondrial biogenesis through PGC-1α phosphorylation and SIRT1/NAD⁺ pathway engagement. AICAR has been famously used to demonstrate the "exercise mimetic" concept in pharmacological research.
Research Applications¶
- Primary: AMPK signaling — cellular energy sensing, metabolic reprogramming, exercise mimetic pharmacology
- Secondary: Glucose metabolism and insulin sensitivity, fatty acid oxidation research, mitochondrial biogenesis and PGC-1α biology
- Model Systems: In vitro (C2C12 myotubes, primary hepatocytes, 3T3-L1 adipocytes), in vivo (exercise performance models, metabolic disease models, AMPK transgenic mice)
Quality Control & Analytical Methods¶
- HPLC: ≥98% purity verification at 214/220 nm (C18 reversed-phase column)
- Mass Spectrometry: ESI-MS for molecular weight confirmation (~258.2 Da)
- Peptide Content: Not applicable (nucleoside analog); HPLC purity by area %
- Endotoxin: <1 EU/mg (LAL assay)
- TFA Content: Not applicable (non-peptide)
Stability & Storage¶
| Condition | Stability |
|---|---|
| -20°C (lyophilized) | 24 months |
| 4°C (lyophilized) | 6 months |
| 25°C (lyophilized) | 1 month |
| Reconstituted (4°C) | 7 days |
| Reconstituted (-20°C) | 30 days |
Key Research References¶
- Corton et al. (1995) — 5-Aminoimidazole-4-carboxamide ribonucleoside: a specific method for activating AMP-activated protein kinase. Eur J Biochem. PMID: 11782219
- Narkar et al. (2008) — AMPK and PPARδ agonists are exercise mimetics. Cell. PMID: 18657498
- Hardie et al. (2012) — AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. PMID: 22436748
Source & Purchase¶
For researchers requiring research-grade AICAR with full analytical documentation including HPLC, LC-MS, and Certificate of Analysis, visit the HK Peptides product page for specifications, bulk pricing, and ordering.
Related Molecules¶
- MOTS-c — Mitochondrial-derived peptide that activates AMPK
- NAD+ — Cellular energy coenzyme, SIRT1 substrate
- SS-31 — Mitochondrial protection peptide
- All Product Specifications
FAQ¶
Q: What purity level is standard for AICAR? A: HK Peptides supplies AICAR at ≥98% purity by HPLC with full COA documentation.
Q: How should AICAR be stored for research use? A: Lyophilized AICAR should be stored at -20°C. Reconstituted solutions at 4°C for short-term use (up to 7 days).