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AICAR with MOTS-c

Mechanism-tag overlap and published literature for AICAR and MOTS-c, pulled verbatim from each Kalios compound profile. Kalios is a literature reference, not a recommendation.

Mechanism overlap

Mechanism tags are verbatim labels on each compound's profile. Generic tags ("peptide", "small-molecule", "research-chemical") are excluded from this overlap view. Tags are descriptive — not an inference about combined effect.

AICAR MOTS-C 1 UNIQUE TAGS 1 UNIQUE TAGS 0 SHARED
AICAR unique ampk-activator-exercise-mimetic
Shared none
MOTS-c unique mitochondrial-derived-exercise-mimetic

Co-administration notes from the literature

Verbatim summary text pulled from each compound's profile data. Researchers studying AICAR and MOTS-c have published these mechanism-level observations. Not a co-administration recommendation.

Evidence level: mechanistic only

MOTS-c activates AMPK through a mitochondrial-derived peptide signaling pathway. AICAR activates AMPK through AMP mimicry. Two different entry points to the same downstream kinase. The combination is sometimes used in exercise-mimetic experimentation but has no controlled head-to-head data.

Quick facts

AICAR

RouteIV (clinical studies) / SubQ / Oral
Half-life~1.5 h IV (parent); intracellular ZMP longer
FDA statusNot approved
WADABanned S4 (Hormone & Metabolic Modulators)
Full AICAR profile →

MOTS-c

RouteSubQ / IP / IM
Half-life~2 hr plasma; hours-days tissue
FDA statusNot approved
WADANot listed
Full MOTS-c profile →

Literature table

Classified references from each compound profile. Click a column header to sort. Click a PMID to open PubMed. Findings are quoted verbatim from each profile's literature_summary; nothing here is added or interpreted.

Year Compound Source Finding
1997AICARMangano DT; Multicenter Study of Perioperative Ischemia Research Group. Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. JAMA. 1997;277(4):325-332. PMID: 9002496. (Meta-analysis of acade… PMID 9002496meta-analysis
2013AICARVan Den Neste E, Cazin B, Janssens A, González-Barca E, Terol MJ, Levy V, Pérez de Oteyza J, Zachee P, Saunders A, de Frias M, Campàs C. Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicentre phase I/II study. Cancer Chemother Pharmacol… PMID 23228967human trial, Phase 1
2008AICARNarkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARδ agonists are exercise mimetics. Cell. 2008;134(3):405-415. PMID: 18674809. (The definitive "exercise in a pill" mouse endurance paper.) PMID 18674809preclinical, in vivo
1997AICARMerrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol. 1997;273(6 Pt 1):E1107-E1112. PMID: 9435525. (Foundational AMPK-activation mechanistic paper.) PMID 9435525preclinical, in vivo
1994AICARSullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett. 1994;353(1):33-36. PMID: 7926017. (Early metabolic-effect c… PMID 7926017preclinical, in vivo
2009AICARWorld Anti-Doping Agency. The 2009 Prohibited List: International Standard. WADA. 2009. (First inclusion of AICAR on the banned list under S4.)regulatory / registry
2014AICARMulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35(6):992-1019. PMID: 25216328. (Broader metabolic-modulator context for comparing AMPK-activating approaches with other diabetes-pharmacology stra… PMID 25216328research article
2011AICARHardie DG. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev. 2011;25(18):1895-1908. PMID: 21937710. (Authoritative AMPK review by a leading AMPK biochemist.) PMID 21937710research article
1999AICARKemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, Witters LA. Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci. 1999;24(1):22-25. PMID: 10087918. (AMPK signaling framework reference.) PMID 10087918research article
1995AICARCorton JM, Gillespie JG, Hawley SA, Hardie DG. 5-Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem. 1995;229(2):558-565. PMID: 7744080. (Methodology establishing AICAR as the canonical AMPK-a… PMID 7744080research article
1984AICARSabina RL, Swain JL, Olanow CW, Bradley WG, Fishbein WN, DiMauro S, Holmes EW. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. J Clin Invest. 1984;73(3):720-730. PMID: 6707200. (Context for AMPD… PMID 6707200research article
2022MOTS-cRamanjaneya M, Jerobin J, Bettahi I, et al. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 2022;23(19):11991. PMID: 36233287. PMID 36233287human study
2022MOTS-cYin X, Jing Y, Chen Q, et al. The intraocular expression of MOTS-c in patients with age-related cataracts: Correlation between MOTS-c and lens mitochondrial DNA levels. Clin Exp Ophthalmol. 2022;50(5):498-506.human study
2018MOTS-cKim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28(3):516-524.e7. PMID: 29983246. PMID 29983246mechanism / discovery
2023MOTS-cKong BS, Lee C, Cho YM. Mitochondrial-encoded peptide MOTS-c, diabetes, and aging-related diseases. Diabetes Metab J. 2023;47(3):315-327. PMID: 36672073. PMID 36672073research article
2021MOTS-cReynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. P… PMID 33473109research article
2018MOTS-cMendelsohn AR, Larrick JW. Mitochondrial-Derived Peptides Exacerbate Senescence. Rejuvenation Res. 2018;21(4):369-373. PMID: 30037300. PMID 30037300research article
2015MOTS-cLee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID: 25738459. DOI: 1… PMID 25738459research article
2013MOTS-cLee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. 2013;24(5):222-228. PMID: 23402768. PMID 23402768research article

Related pair pages

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Frequently asked

Have AICAR and MOTS-c been studied together?

Researchers have published mechanistic-level co-administration discussion of AICAR and MOTS-c. No human co-administration trials are catalogued in the Kalios profiles. The pair page lists each compound's classified literature; full citations sit on each individual profile.

What mechanisms do AICAR and MOTS-c share?

AICAR and MOTS-c do not share a specific mechanism tag on their Kalios profiles. They appear on the same pair page because at least one profile lists the other in its co-administration data.

What is the FDA status of AICAR and MOTS-c?

AICAR: Not approved. MOTS-c: Not approved. FDA-status text is pulled verbatim from each compound profile. See /fda-pcac-2026.html for the broader FDA Pharmacy Compounding Advisory Committee context.

Where can I find the full research on AICAR and MOTS-c?

Full citation lists, dosing tables from the literature, reconstitution data, and the FDA / WADA status are on the individual compound profiles: the AICAR profile and the MOTS-c profile. The Kalios Stack Research Tool hub lists every compound covered.

Last updated: April 2026