AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) is a small-molecule research reagent used to interrogate cellular energy-sensing and metabolic signaling networks. In laboratory systems, AICAR is employed as a tool compound to activate AMP-activated protein kinase (AMPK) and to profile downstream changes in substrate utilization, stress-response signaling, transcriptional programs, and cell-cycle regulation in cell culture and in vivo animal models.

AICAR is frequently used in experimental workflows that quantify AMPK-associated effects on glucose transport, inflammatory pathway outputs, and proliferation/survival endpoints under controlled conditions. All descriptions are provided for mechanistic and preclinical research context only.

Source: PubChem

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

• AMPK activation assays for pathway mapping, phosphorylation-state profiling, and metabolic flux experiments.
• Glucose transport research in muscle models, including insulin-stimulated uptake and GLUT-4 content/trafficking endpoints.
• Inflammation and immune-signaling studies evaluating AMPK-linked modulation of macrophage signaling and cytokine outputs.
• Cell-cycle and apoptosis research assessing AMPK-associated p38 MAPK signaling, p21-related checkpoints, and caspase-linked pathways.
• Vascular biology experiments evaluating smooth muscle proliferation and leukocyte rolling/adhesion mechanisms in preclinical models.
• Reproductive biology tool studies evaluating AMPK-linked regulation of spermatozoa energy metabolism and motility endpoints in species-specific systems.

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.

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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