AICAR 50mg

AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) is a synthetic nucleoside analog and AMP mimetic that functions as an activator of AMP-activated protein kinase (AMPK) in laboratory models. After cellular uptake, AICAR is phosphorylated to form ZMP (AICA ribonucleotide), which structurally resembles AMP and engages AMPK-associated regulatory pathways. AMPK is a central energy-sensing enzyme involved in coordinating cellular responses to changes in energy availability.

Most published research focuses on how AICAR-induced AMPK activation alters metabolic signaling networks, including pathways governing glucose transport, lipid oxidation, mitochondrial biogenesis, and inflammatory mediator expression. Experimental systems commonly include cultured muscle cells, adipocytes, immune cells, and various animal models. Within these frameworks, AICAR is used as a research tool compound to explore energy homeostasis, metabolic adaptation, and signal transduction mechanisms under controlled laboratory conditions.

Sequence: 5-aminoimidazole-4-carboxamide ribonucleoside
Molecular Formula: C₉H₁₅N₄O₈P
Molecular Weight: 338.213 g/mol
PubChem CID: 65110
CAS Number: 3031-94-5
Synonyms: AICA ribonucletotide, Z-nucleotide

Research applications for AICAR are primarily conducted in vitro and in animal models to evaluate AMPK activation–dependent cellular responses. Study designs typically compare AICAR-treated samples to untreated or vehicle-treated controls, and in some cases to genetic AMPK-modified models, to determine pathway-specific effects.

Commonly measured endpoints include AMPK phosphorylation status, downstream targets such as ACC (acetyl-CoA carboxylase) phosphorylation, GLUT4 expression and translocation assays, glucose uptake measurements, lipid oxidation markers, and mitochondrial activity indicators. In immune and inflammatory models, investigators may assess NF-κB signaling, cytokine expression profiles, and macrophage activation markers relative to controls. In oncology-related cell systems, endpoints often include cell cycle markers, apoptosis-associated proteins such as caspases, and proliferation assays under controlled experimental conditions.

Across cardiovascular and vascular biology models, research may evaluate smooth muscle cell proliferation markers, endothelial function indicators, and immune cell recruitment parameters. In reproductive cell studies, endpoints can include sperm motility measurements, ATP levels, and metabolic enzyme activity assays.

All findings are interpreted as mechanistic observations within laboratory and preclinical contexts. Results are limited to in vitro and animal research settings and do not imply therapeutic, preventive, or clinical use.

Core target node: AMPK functions as a central integrator of cellular energy status, coordinating metabolic adaptation through downstream regulation of substrate transport, mitochondrial activity, and transcriptional responses to energetic stress.

Metabolic signaling interface: In preclinical muscle models, AMPK activation has been evaluated alongside insulin-linked signaling readouts and GLUT-4-associated endpoints to characterize glucose uptake regulation under defined experimental conditions.

Inflammation-associated signaling: AMPK activation is commonly explored for effects on NF-κB-associated transcriptional programs and macrophage inflammatory outputs, supporting mechanistic studies in adipose- and colitis-related models.

Stress-response and cell fate pathways: In cultured cells, AMPK activation can intersect with p38 MAPK signaling and p21 accumulation, and may engage caspase-linked apoptosis machinery depending on model context and experimental design.

Vascular remodeling: AMPK-linked cell-cycle regulation has been studied in vascular smooth muscle proliferation models, and preconditioning paradigms have been used to evaluate leukocyte rolling/adhesion endpoints in microcirculation research.

In mouse models, AICAR has been used as an AMPK-activating tool compound to evaluate adipose inflammatory signaling and insulin resistance-associated endpoints, including studies describing dependence on myeloid SIRT1 in specific experimental settings^[1]. Additional preclinical work reports AMPK activation effects on inflammatory response markers and metabolic disorder phenotypes in particulate exposure models^[2].

In rat skeletal muscle models, AICAR has been used to compare exercise-linked signaling to AMPK activation, including insulin-stimulated glucose uptake and GLUT-4 content endpoints^[3]. In cell culture and animal models, AICAR-mediated AMPK activation has been evaluated in proliferation and survival assays in multiple cell lines, including studies reporting AMPK-associated growth control and stress susceptibility effects^{[4], [5]}.

In inflammation-focused models, AICAR has been used to assess immune signaling mechanisms (including NF-κB-associated macrophage signaling and TH1/TH17-type cytokine outputs) in preclinical colitis paradigms^[9]. In vascular biology, AMPK activation has been evaluated for effects on vascular smooth muscle proliferation via cell-cycle regulation^[10], and microcirculation models have been used to study leukocyte rolling/adhesion endpoints in AICAR-associated preconditioning experiments^[14].

In reproductive biology tool studies, AMPK activators including AICAR have been used in species-specific systems to evaluate spermatozoa energy metabolism and motility endpoints^{[12], [13]}.

AICAR inhibits clonal growth of glioma (C6) and prostate cells.
Source: Journal of Biological Chemistry

AMPK activators, like AICAR, influence a number of pathways that can impact cancer growth.
Source: PubMed

AICAR is supplied as a research reagent for laboratory experimentation. Product identity and purity are commonly verified using standard analytical techniques such as HPLC and mass spectrometry (MS). Researchers should select solvent systems and storage conditions appropriate for nucleoside analogs and for compatibility with the intended in vitro or in vivo protocol.

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Spencer Gaskin, M.D., Ph.D. is an American Board of Internal Medicine certified cardiologist and medical practitioner. His expertise of Internal medicine and cardiology sources from UT Southwestern Cardiology, Washington University Interventional Cardiology, and the Mid America Heart Institute. Dr. Gaskin led a study that examined the prevention of Postischemic Leukocyte Rolling and Adhesion via preconditioning with AICAR.

Spencer Gaskin, M.D., Ph.D. is being referenced as one of the leading scientists involved in the research and development of AICAR. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Dr. Gaskin is listed in [14] under the referenced citations.

1. Z. Yang et al., “The full capacity of AICAR to reduce obesity-induced inflammation and insulin resistance requires myeloid SIRT1,” PloS One, vol. 7, no. 11, p. e49935, 2012.
2. K. Pan et al., “AMPK activation attenuates inflammatory response to reduce ambient PM2.5-induced metabolic disorders in healthy and diabetic mice,” Ecotoxicol. Environ. Saf., vol. 179, pp. 290–300, Sep. 2019.
3. N. Jessen, R. Pold, E. S. Buhl, L. S. Jensen, O. Schmitz, and S. Lund, “Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles,” J. Appl. Physiol. Bethesda Md 1985, vol. 94, no. 4, pp. 1373–1379, Apr. 2003.
4. J. Zhuge, “Overexpression of CYP2E1 induces HepG2 cells death by the AMP kinase activator 5’-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR),” Cell Biol. Toxicol., vol. 25, no. 3, pp. 253–263, Jun. 2009.
5. R. Rattan, S. Giri, A. K. Singh, and I. Singh, “5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase,” J. Biol. Chem., vol. 280, no. 47, pp. 39582–39593, Nov. 2005.
6. M. M. H. Yung, H. Y. S. Ngan, and D. W. Chan, “Targeting AMPK signaling in combating ovarian cancers: opportunities and challenges,” Acta Biochim. Biophys. Sin., vol. 48, no. 4, pp. 301–317, Apr. 2016.
7. W. G. Kim, H.-J. Choi, T. Y. Kim, Y. K. Shong, and W. B. Kim, “The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside was mediated by p38 mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells,” Korean J. Intern. Med., vol. 29, no. 4, pp. 474–481, Jul. 2014.
8. X.-W. Peng, H.-H. Zhou, J. Dai, and L. Zhang, “[Advances on the anti-inflammatory and protective effect of AMPK activators],” Sheng Li Xue Bao, vol. 71, no. 2, pp. 319–326, Apr. 2019.
9. A. Bai et al., “Novel anti-inflammatory action of 5-aminoimidazole-4-carboxamide ribonucleoside with protective effect in dextran sulfate sodium-induced acute and chronic colitis,” J. Pharmacol. Exp. Ther., vol. 333, no. 3, pp. 717–725, Jun. 2010.
10. M. Igata et al., “Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression,” Circ. Res., vol. 97, no. 8, pp. 837–844, Oct. 2005.
11. M. Sakai, S. Kobori, A. Miyazaki, and S. Horiuchi, “Macrophage proliferation in atherosclerosis,” Curr. Opin. Lipidol., vol. 11, no. 5, pp. 503–509, Oct. 2000.
12. P. Thuwanut, P. Comizzoli, K. Pruksananonda, K. Chatdarong, and N. Songsasen, “Activation of adenosine monophosphate-activated protein kinase (AMPK) enhances energy metabolism, motility, and fertilizing ability of cryopreserved spermatozoa in domestic cat model,” J. Assist. Reprod. Genet., May 2019.
13. Z. Zhu et al., “5’-AMP-Activated Protein Kinase Regulates Goat Sperm Functions via Energy Metabolism In Vitro,” Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol., vol. 47, no. 6, pp. 2420–2431, 2018.
14. F. Spencer Gaskin, Kazuhiro Kamada, Mozow Yusof, William Durante, Garrett Gross & Ronald J. Korthuis (2009) AICAR Preconditioning Prevents Postischemic Leukocyte Rolling and Adhesion: Role of KATP Channels and Heme Oxygenase, Microcirculation, 16:2, 167-176, DOI: 10.1080/10739680802355897

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The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.

For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.