Aicar Usa

AICAR USA Supply Overview & Academic Research Standards

Sourcing high-purity AICAR USA research material is essential for investigators studying cellular energy homeostasis, purine biosynthesis, and metabolic signaling pathways. AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide, also known as Acadesine) is an adenosine analog that functions as a direct intracellular activator of AMP-activated protein kinase (AMPK). Academic and private laboratories in the United States require analytical-grade compounds to ensure reproducible quantitative assays across cell lines and rodent models.

To maintain internal validity in preclinical studies, investigators must procure research reagents synthesized under stringent quality controls. Substandard or degraded material can introduce confounding variables, such as unreacted chemical precursors or excessive bacterial endotoxins, which disrupt delicate cellular pathways. PX1 Research addresses these requirements by supplying USA-manufactured AICAR verified through third-party ISO 17025 accredited testing laboratories.

Chemical Structure and Molecular Mechanism of AICAR (Acadesine)

AICAR is a nucleoside analog structurally related to adenosine. Upon cellular uptake via nucleoside transporters, AICAR is phosphorylated by adenosine kinase into its active monophosphorylated form, ZMP (5-aminoimidazole-4-carboxamide ribonucleotide). ZMP acts as an AMP mimetic, binding directly to the gamma subunit of AMPK without significantly altering physiological intracellular ATP, ADP, or AMP concentrations.

Binding of ZMP induces a conformational change in the heterotrimeric AMPK complex, promoting the phosphorylation of Threonine-172 (Thr-172) on the alpha catalytic subunit by upstream kinases such as LKB1 (liver kinase B1). This activation shifts cellular metabolism from anabolic pathways (energy consumption) to catabolic pathways (ATP generation). In vitro research indicates that ZMP activation of AMPK downregulates fatty acid synthesis through the inhibitory phosphorylation of acetyl-CoA carboxylase (ACC) while concurrently stimulating fatty acid oxidation and glucose uptake.

Researchers evaluating purine metabolic pathways also utilize AICAR to investigate intermediate steps in de novo purine nucleotide synthesis. Because ZMP is a natural intermediate in the purine pathway, its exogenous administration allows for precise downstream mapping of enzymatic kinetics and metabolic flux in specialized cell lines.

Preclinical Research Findings: Metabolic Regulation & Energy Homeostasis

Preclinical studies using rodent models have extensively documented the metabolic impact of pharmacological AMPK activation via AICAR. In murine models of metabolic dysregulation, administration of AICAR has been shown to enhance insulin sensitivity, suppress hepatic gluconeogenesis, and promote glucose transporter 4 (GLUT4) translocation in skeletal muscle tissue.

In vitro data indicate that AICAR-mediated AMPK activation suppresses the expression of key gluconeogenic enzymes in hepatocytes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). By downregulating these targets, researchers can observe glucose output regulation independently of insulin signaling cascades. These mechanistic insights make AICAR an important tool in AMPK pathway modulators research.

Furthermore, preclinical animal studies demonstrate that long-term activation of AMPK by AICAR leads to remodeled lipid profiles, increased fatty acid oxidation in oxidative muscle fibers, and diminished systemic inflammation markers. These observed effects occur primarily through AMPK-dependent downregulation of SREBP-1c and mammalian target of rapamycin complex 1 (mTORC1) signaling.

AICAR in Mitochondrial Biogenesis and Exercise Mimetic Studies

A prominent area of investigation involving AICAR centers on mitochondrial biogenesis and transcription factor modulation. AMPK activation by ZMP stimulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a master regulator of mitochondrial gene expression. In vitro assays demonstrate that AICAR treatment upregulates nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), leading to increased mitochondrial mass and elevated oxidative phosphorylation capacity.

In sedentary rodent models, sustained administration of AICAR demonstrated a measurable increase in running endurance and oxidative muscle fiber composition without prior physical training, leading researchers to classify AMPK activators as exercise mimetics in preclinical literature. These findings highlight the utility of AICAR for studying neuromuscular adaptations, sarcopenia models, and metabolic endurance mechanisms in vitro.

Investigating the synergies between mitochondrial biogenesis and cellular longevity pathways remains a vibrant domain within our broader research library. By providing reliable AICAR reagents, PX1 Research enables investigators to isolate the precise transcription cascades governing cellular bioenergetics.

Comparative Analysis: AICAR vs. Other Metabolic Modulators

When designing metabolic research protocols, investigators often contrast AICAR with other signaling modulators, synthetic ligands, and mitochondrial peptides. Understanding the distinct molecular targets of each compound is essential for selecting the appropriate tool for specific experimental endpoints.

AICAR acts directly on the AMPK gamma subunit via its phosphorylated metabolite ZMP. In contrast, compounds such as GW501516 operate through an entirely different pathway, acting as a selective agonist for the peroxisome proliferator-activated receptor delta (PPARδ). While AICAR stimulates acute energy sensing and intracellular substrate utilization via kinase phosphorylation, PPARδ agonists induce transcriptional changes governing fatty acid transport and oxidation over longer time horizons.

Another relevant comparison involves MOTS-c, a mitochondrially derived peptide that regulates metabolic homeostasis through nuclear translocation and gene expression modulation under metabolic stress. While both AICAR and MOTS-c mitochondrial research targets involve downstream AMPK phosphorylation, MOTS-c acts via systemic peptide-signaling mechanisms rather than functioning as a direct small-molecule nucleoside precursor. Additionally, synthetic Rev-ErbA agonists like SR9009 modulate circadian rhythm genes to alter metabolic rate, offering a distinct pathway from AICAR's direct purine-pathway interaction.

Analytical Purity Protocols: RP-HPLC and ESI-MS Testing

Ensuring the validity of experimental outcomes requires strict chemical verification of all laboratory compounds. Research-grade AICAR from PX1 Research undergoes rigorous testing using Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) and Electrospray Ionization Mass Spectrometry (ESI-MS) to guarantee chemical identity and purity.

RP-HPLC analysis isolates the primary molecule from potential synthesis byproducts, structural isomers, and baseline impurities. A standard specification of ≥98% purity by HPLC area normalization ensures that non-target chemical species do not interfere with cell culture receptors or enzymatic assays.

Mass spectrometry (ESI-MS) confirms the exact molecular weight and isotopic distribution of the AICAR molecule (C9H14N4O5, monoisotopic mass ~258.23 g/mol). Every lot produced is matched against theoretical molecular spectra to prevent batch-to-batch variation. Researchers can access these primary analytical data sets via our comprehensive catalog of all peptides and small molecules.

Endotoxin Screening and Sterility Standards for In Vitro Assays

In cell culture and animal model research, bacterial endotoxins (lipopolysaccharides, LPS) represent a major source of experimental error. Trace levels of endotoxin can trigger Toll-like receptor 4 (TLR4) activation, inducing unwanted inflammatory cytokine release (such as TNF-α, IL-6, and IL-1β) that confounds metabolic data.

PX1 Research subjects every lot of domestic AICAR to strict endotoxin quantification using Chromogenic Limulus Amebocyte Lysate (LAL) testing. Materials are certified to contain less than 0.01 EU/mg, well below the threshold capable of inducing non-specific immune activation in vitro.

All solid products are synthesized, purified, and packaged in GMP-compliant facilities adhering to ISO 9001 and ISO 17025 laboratory standards. Lyophilized vials are sealed under an inert gas atmosphere to preserve compound integrity during transit and storage.

Laboratory Reconstitution Protocols and Solubility Metrics

AICAR is supplied as a lyophilized crystalline powder. Achieving complete solubilization is critical for preparing accurate working stock concentrations for cellular assays. AICAR exhibits favorable solubility in aqueous buffers such as Phosphate-Buffered Saline (PBS, pH 7.2) up to approximately 10 mg/mL with mild sonication or vortexing.

For higher concentration stock solutions (up to 50 mg/mL), dimethyl sulfoxide (DMSO) or sterile water for injection (WFI) may be used. When preparing stocks in DMSO, researchers should ensure final vehicle concentrations in culture media do not exceed 0.1% to 0.5% (v/v) to avoid vehicle-induced cytotoxicity.

Once reconstituted in aqueous solutions, AICAR working aliquots should be used immediately or stored at -80°C to prevent hydrolysis of the riboside linkage. Repeated freeze-thaw cycles must be avoided, as thermal fluctuations accelerate physical breakdown and drop operational concentration.

Storage Conditions and Aliquoting Best Practices

Proper long-term storage of solid and liquid AICAR stock is essential to preserve enzymatic activity and compound stability. Upon receipt of shipment, lyophilized AICAR vials should be stored in a desiccated environment at -20°C or -80°C, protected from direct light exposure.

Under desiccated storage at -20°C, solid AICAR maintains stable potency for up to 24 months. If stored at room temperature during active laboratory handling, exposure should be minimized to avoid moisture absorption (hygroscopic gain).

When preparing experimental aliquots, researchers should dissolve the solid material in a suitable sterile solvent under a laminar flow hood, divide the solution into single-use microcentrifuge tubes, freeze immediately at -80°C, and discard any unused portion after thawing to guarantee concentration consistency.

Sourcing High-Purity Research Compounds from US Facilities

Procuring research compounds from domestic US suppliers minimizes supply chain disruptions, reduces transit time, and ensures compliance with domestic quality frameworks. PX1 Research operates distribution centers in California and Arizona, facilitating same-day dispatch for laboratory orders placed Monday through Friday.

Domestic manufacturing and warehousing insulate research institutions from foreign regulatory delays, customs holds, and unpredictable degradation during prolonged international transit. Every batch shipped from PX1 Research includes batch-matched COAs linked directly to third-party testing metrics.

Academic laboratories, biotechnology firms, and institutional researchers seeking scalable procurement options can access specialized pricing structures through our dedicated wholesale lab portal.