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Exercise mimetics: AICAR, SLU-PP-332 and MOTS-c

Updated 15 Oct 2026 Author: About 14 min read Drafted with the help of AI; sources and claims checked separately.

This guide shows the promising side as animal studies give it, but for every finding it says that it has not been studied in humans and why a mouse result may not hold in people.

In short. An exercise mimetic is a substance that makes muscle respond as if it had trained: the body, so to speak, thinks you went for a run. In mice, AICAR increased the running distance of sedentary mice by about 44% [1]C, SLU-PP-332 by about 45% [11]C, and MOTS-c improved the performance of young and old mice [20]C. None has been studied in humans as an exercise mimetic [25]regulator [38]E, not peer-reviewed. WADA already bans AICAR and MOTS-c by name, and SLU-PP-332 is named on the list from 1 Jan 2027; class S0 already bans non-approved substances that the list does not otherwise cover [31, 32]regulator.

The key difference in short

Three substances, three different routes. AICAR activates AMPK, the energy sensor of the cell [1]C. SLU-PP-332 activates the ERR receptors that run the muscle gene programme of endurance training [11]C. MOTS-c is a peptide coded by the mitochondria's own genome and made by the body itself [19]C.

How much is known about humans differs. AICAR has been given to people into a vein in heart surgery and in metabolic studies, but not as an exercise mimetic [2]B [6, 7]A. There is no human study of SLU-PP-332 at all [38]E, not peer-reviewed. According to the FDA, MOTS-c has not been given to humans, but the first placebo-controlled trial is under way [25]regulator [35]E, not peer-reviewed.

All three lack a marketing authorisation in the EU [34]regulator, and none is named in the Fimea list of medicines [33]regulator.

What is an exercise mimetic?

The term became known in 2008, when researchers at the Salk Institute in the US published a study titled "AMPK and PPARdelta agonists are exercise mimetics". Four weeks of AICAR increased the running endurance of sedentary mice without training [1]C.

The idea is attractive: if a medicine could switch on the endurance programme of muscle, it might help people who cannot exercise, for example because of illness or old age. According to a review, however, exercise mimetics have mostly been described in animal and lab studies, with limited translation into humans [29].

None of the three substances in this guide is an approved medicine in the EU [34]regulator.

Comparison table: AICAR vs SLU-PP-332 vs MOTS-c

The table also shows GW501516 (cardarine) as background; its development was stopped for safety reasons. The letter is the evidence level, not a result. Trial counts from the ClinicalTrials.gov registry on 15 Oct 2026.

Sources read on 15 Oct 2026.
SubstanceWhat it isIn miceIn humansWADA and Finland
AICAR (acadesine)AMPK activator, a nucleoside [10]Running distance about 44% longer without training [1]CInto a vein in heart surgery and metabolic studies, not as an exercise mimetic; 5 trials in the registry [6, 7]A [38]E, not peer-reviewedWADA S4.4.1 [31]regulator; not in the Fimea list of medicines [33]regulator
SLU-PP-332ERR receptor agonist, a small synthetic molecule, not a peptide [11]C [18]DRan about 70% longer and 45% further [11]CNo studies; 0 in the registry [38]E, not peer-reviewedNamed on the WADA list from 1 Jan 2027 [32]regulator; not in the Fimea list of medicines [33]regulator
MOTS-cA 16 amino acid peptide coded by the mitochondria [19]CBetter performance in young, middle-aged and old mice [20]CNot given to humans [25]regulator; 1 ongoing phase 2 trial [35]E, not peer-reviewedWADA S4.4.1 [31]regulator; not in the Fimea list of medicines [33]regulator
GW501516 (cardarine)PPAR-delta receptor agonist [1]CRunning capacity improved only with training [1]CBlood lipids changed in a 12-week trial [26]A; development stopped [27]WADA S4.4.1 [31]regulator; annex 1 A of the Fimea list of medicines [33]regulator

Read more: AICAR (acadesine): full substance page | SLU-PP-332: full substance page | MOTS-c: full substance page

How they work: AMPK, ERR receptors and mitochondria

AICAR activates the enzyme AMPK, the energy sensor of the cell, which exercise also activates [1]C [10]. In mice, AICAR switched on metabolic genes in muscle linked to endurance [1]C. In human muscle, AICAR increased glucose uptake, but AMPK activity did not rise in the muscle samples, so the effect may run by another route [2]B.

SLU-PP-332 activates all three estrogen-related receptors (ERR alpha, beta and gamma), most strongly ERR alpha. In mice it switched on the same gene programme as a single endurance workout, and the gain in running capacity required the ERR alpha receptor in muscle: in mice whose muscle lacked ERR alpha, no effect was seen [11]C.

MOTS-c is a 16 amino acid peptide coded in the 12S rRNA gene of the mitochondria. In mouse and cell studies it inhibited the folate cycle and the linked production of purines, which activated AMPK; its main target appeared to be skeletal muscle [19]C. In a 2026 study, MOTS-c improved the energy efficiency of mouse muscle mitochondria, and the effect depended on both PGC-1alpha and AMPK [22]C. According to the FDA, the actual molecular targets of MOTS-c are unknown [25]regulator.

For comparison, GW501516 activates the PPAR-delta receptor, which increases fat burning in muscle; in the same 2008 study, AICAR and GW501516 strengthened each other's effect in muscle cells [1]C.

Promising, but so far only in animals

These findings are why people talk about exercise mimetics. Each item says what was found, what it would mean for a person if it held, why it may not hold and where research stands now.

  • AICAR, endurance without training (no human studies as an exercise mimetic). What was found: four weeks of AICAR injections into the abdominal cavity made sedentary mice run about 23% longer and 44% further than controls [1]C. In old mice, a month of AICAR prevented the 24.5% decline in running capacity seen in controls, and muscle contraction force was 26.4% higher [8]C. If it held in humans: an inactive or older person could get some of the benefits of endurance training without training. Why it may not carry over: in the human studies used here AICAR was given into a vein as infusions lasting from one to several hours [2, 4, 5]B, and in mice the brain benefits turned harmful within two weeks (below) [9]C. Evidence now: several mouse studies by different groups; no registered human trial as an exercise mimetic [38]E, not peer-reviewed.
  • SLU-PP-332, endurance and metabolism (no human studies). What was found: after a week of treatment, mice ran about 70% longer and 45% further than controls (6 mice per group), and had more oxidative type IIa muscle fibres [11]C. In obese mice, energy expenditure and fat burning increased, fat mass fell and insulin sensitivity improved [12]C. In old mice, eight weeks of treatment reversed age-related mitochondrial damage and inflammation in the kidneys [14]C, and in a mouse model of heart failure it improved heart pumping and survival [13]C. If it held in humans: a new way to treat obesity, diabetes, heart failure and age-related muscle weakness. Why it may not carry over: the substance is not absorbed by mouth, and the mice were injected into the abdominal cavity [16]C; members of the developing group hold shares in a company developing ERR drugs [11, 16]C; there are no long-term safety data. Evidence now: several mouse studies, most from the same group; in human muscle cells in the laboratory it reduced oxidative stress [15]D; it has not been given to humans, and the registry lists 0 trials [38]E, not peer-reviewed.
  • MOTS-c, performance and metabolism (no human studies). What was found: in mice MOTS-c prevented insulin resistance and weight gain caused by age and a high-fat diet [19]C. It improved the physical performance of young, middle-aged and old mice, and treatment three times a week started very late in life increased physical capacity [20]C. In diabetes models it reduced ageing of pancreatic islet cells [24]C. If it held in humans: age-related loss of function and type 2 diabetes could be slowed. Why it may not carry over: according to the FDA, the studies have been done only in rodents and the dose-response relationship has not been studied [25]regulator; in human stem cells MOTS-c reduced cell division and increased the expression of senescence-related genes [23]D. Evidence now: several mouse studies; the first human trial, phase 2 in prediabetes, is recruiting [35]E, not peer-reviewed.
  • What to expect: primary data collection of the MOTS-c trial is estimated to end in February 2027 [35]E, not peer-reviewed. There is no registered human exercise mimetic trial of AICAR or SLU-PP-332 [38]E, not peer-reviewed.

Effectiveness in humans: what has been studied

AICAR: in healthy men (29 people), AICAR given into a vein doubled muscle glucose uptake over three hours, while cycling increased it 4.7-fold; whole-body glucose use rose by 7% [2]B. The effect weakened with age: in young men glucose uptake almost tripled, in older men less [3]B. In men with type 2 diabetes (10 people), AICAR reduced glucose output by the liver and lowered blood glucose [4]B. In another study, AICAR did not increase glucose uptake during an insulin infusion [5]B.

In heart surgery, acadesine (AICAR) was studied in randomised trials. In a meta-analysis of five trials with 4,043 bypass patients, heart attacks around the operation fell by 27% [6]A. A larger phase 3 trial (3,080 randomised) was stopped, however, because no benefit was expected: the main outcome occurred in 5.1% on acadesine and 5.0% on placebo [7]A.

MOTS-c: in humans only the body's own MOTS-c has been measured. In ten young men, cycling increased MOTS-c in muscle and blood [20]B. In a randomised study of 30 people, blood MOTS-c seemed to rise after endurance exercise, but the change was not statistically certain, and levels were not linked to fitness or muscle strength [21]A. People with type 2 diabetes had lower blood MOTS-c than healthy controls [24]B.

SLU-PP-332: there are no human data. According to a systematic review, all information comes from animal and cell studies, and human trials are needed to establish efficacy and safety [39].

Head-to-head comparison: no studies

A head-to-head comparison is missing: in no study we found were AICAR, SLU-PP-332 and MOTS-c compared with each other in the same experiment (as of 15 Oct 2026). The percentages from mouse studies cannot be compared, because mouse strains, treadmill tests, treatment length and route differed [1, 11, 20]C.

The closest to a direct comparison is the 2008 study that tested AICAR and the PPAR-delta agonist GW501516 with the same methods: GW501516 improved running capacity only together with training, AICAR also without it [1]C.

Why a mouse result may not carry over to humans

  • Human muscle responds less. In healthy men, AICAR increased muscle glucose uptake less than cycling did, and AMPK activity did not rise [2]B, and in older men the effect was smaller [3]B.
  • The benefit may be short-lived. In mice, AICAR increased new brain cells at one week much as running did, but at two weeks the effect turned around: the increase stopped and genes linked to cell death and inflammation rose. Running kept the benefit [9]C.
  • Route. In the mouse studies the substances were injected into the abdominal cavity [1, 11]C [20]C, and SLU-PP-332 is not absorbed by mouth [16]C.
  • Muscle may not be the source. In humans doing one-legged knee extension exercise, MOTS-c in the blood passing through the muscle did not change, suggesting that the MOTS-c that rises during exercise does not come from muscle [22]B.
  • Exercise is more than one signal. According to the title of a 2026 review, exercise pills cannot mimic the overall effect of exercise on the body [30].
  • Small groups and the same research group. The SLU-PP-332 running study had 6 mice per group, and most studies come from the developing group [11, 12, 16]C.

Harms and safety side by side

AICAR: given into a vein it raised the heart rate of healthy people more than placebo and lowered blood pressure, most likely by widening blood vessels [5]B. According to a review, no serious toxicity of acadesine was seen in healthy people or in bypass surgery [10]. Long-term use has not been studied.

SLU-PP-332: in a ten-day injection study in mice, no overt toxicity was seen, and blood counts and electrolytes were normal [11]C. There are no human safety data at all [38]E, not peer-reviewed.

MOTS-c: the FDA found no clinical studies and no human exposure data by any route, so the risks for humans are unknown; there are no carcinogenicity studies [25]regulator. In human stem cells MOTS-c increased the expression of genes linked to senescence and inflammation [23]D.

A cautionary example, GW501516 (cardarine): according to a review, its development was abandoned for safety reasons [27]. In mice given a cancer-causing substance, GW501516 led within two months to rapidly spreading stomach cancers [28]C. Before it was stopped it was studied in humans: over 12 weeks HDL cholesterol rose by up to 16.9% and triglycerides fell by 16.9% [26]A. The example shows that a promising animal and blood lipid result says nothing about long-term safety.

Read more: Peptide side effects and safety | How to read a certificate of analysis (COA)

Doses in studies

None of the three has approved dosing, because none is an approved medicine [34]regulator. None has been given to humans as an exercise mimetic, so there is no human dose that mimics exercise.

In the human AICAR studies the substance was given under study conditions as an infusion into a vein, lasting from one to several hours [2, 4, 5]B [6]A. In the ongoing MOTS-c trial, the substance is injected under the skin once a day for 12 weeks, but the registry does not give the dose [35]E, not peer-reviewed. Mouse doses cannot be converted into human doses.

Read more: Dosing: substances with doses studied in humans

Taken orally or injected?

SLU-PP-332 is not absorbed by mouth; that is why its developers made the chemically different SLU-PP-915, which is absorbed and improved running capacity in mice in the same way when given by mouth [16]C. In mice SLU-PP-915 also strengthened the effect of exercise training on muscle mitochondrial genes [16]C.

AICAR has been given to humans into a vein [2, 4, 5]B [7]A. MOTS-c is a peptide, and both in mouse studies and in the ongoing human trial it was injected [20]C [35]E, not peer-reviewed. There are no published studies of MOTS-c taken by mouth (as of 15 Oct 2026).

In whom have they been studied?

This is a list of the groups studied, not a recommendation for anyone.

  • AICAR: bypass surgery patients [6, 7]A, healthy men and men with type 2 diabetes [2, 3, 4]B, and in the registry patients with chronic lymphocytic leukaemia [38]E, not peer-reviewed.
  • SLU-PP-332: only mice [11]C and human muscle cells in culture [15]D.
  • MOTS-c: the body's own MOTS-c has been measured in people exercising and in people with diabetes [20, 21, 24]B; a trial in adults with prediabetes and overweight is under way [35]E, not peer-reviewed. CB4211, modified from MOTS-c, was studied in a phase 1 trial in healthy people and people with fatty liver disease, but no results are in the registry [36, 37]E, not peer-reviewed.
  • Athletes: AICAR and MOTS-c are banned at all times, SLU-PP-332 is named on the list from 1 Jan 2027, and class S0 probably covers it already [31, 32]regulator.

Does a pill replace exercise, or can it be combined with exercise?

Based on mouse studies, exercise is not replaced. In the 2008 study GW501516 improved running capacity by 60% to 75% only when the mice also trained [1]C. SLU-PP-915 strengthened the effect of training on muscle genes [16]C. The brain benefits of AICAR disappeared within two weeks, those of running did not [9]C.

In humans the combination has not been studied for any of the substances [38]E, not peer-reviewed. Cycling increased muscle glucose uptake more than twice as much as AICAR [2]B.

The same active substance under different names?

  • AICAR and acadesine are the same substance, AICA riboside [10]. Heart surgery trials used the name acadesine [6, 7]A, exercise mimetic studies the name AICAR [1]C.
  • MOTS-c and CB4211 are not the same substance: according to the company, CB4211 is an enhanced analogue modified from MOTS-c [37]E, not peer-reviewed. CB4211 results cannot be carried over to MOTS-c sold online.
  • SLU-PP-332 and SLU-PP-915 are different molecules that activate the same ERR receptors [16]C. On the WADA 2027 list both and related substances are named [32]regulator.

Marketing authorisation, Finnish law and doping: WADA 2026 and 2027

EU: the European Medicines Agency medicines data (14 Oct 2026) contain no medicine whose active substance is AICAR (acadesine), SLU-PP-332, MOTS-c or GW501516 [34]regulator. In the United States, the FDA proposed not adding MOTS-c to the list of substances pharmacies may compound with [25]regulator.

Finland: the Fimea list of medicines (230/2025) does not name AICAR, SLU-PP-332 or MOTS-c. Annex 1 A includes GW-501516 (cardarine) and SR9009 [33]regulator.

Sport: class S4.4.1 (metabolic modulators) of the WADA 2026 Prohibited List names AICAR and MOTS-c as AMPK activators and GW501516 as a PPAR-delta agonist. Class S4 is banned at all times, also out of competition [31]regulator. SLU-PP-332 is not named on the 2026 list, but its class S0 always bans non-approved substances that the list does not otherwise cover [31]regulator; in addition, in the 2027 list approved by WADA on 10 Sep 2026, "SLU-PP-332, SLU-PP-915 and related substances" have been added to class S4.4.1; the list is in force from 1 Jan 2027 [32]regulator. Doping laboratories have already published the metabolites of SLU-PP-332 for detection [17, 18]D.

This is not legal advice.

Read more: Peptides and the law in Finland | Are peptides legal in Europe? | Disclaimer

What speaks against

Studies that speak against or weaken the promising results:

  • The large AICAR heart surgery trial was stopped for futility, although the earlier meta-analysis was promising [6, 7]A.
  • AICAR given into a vein did not increase human muscle glucose uptake during an insulin infusion [5]B.
  • The brain benefits of AICAR in mice turned around within two weeks [9]C.
  • MOTS-c impaired human stem cell function and, as a pretreatment, did not improve the mouse kidney [23]D.
  • The body's own MOTS-c was not linked to fitness or strength in humans [21]A, and muscle may not be its source [22]B.
  • Research on SLU-PP-332 comes almost entirely from one group with financial ties to ERR drugs [11, 16]C.
  • One MOTS-c study on bone fractures has been retracted and is not used on this page.

What we do not know yet

  • Whether any of these substances improves human endurance or health as an exercise mimetic: there are no studies [38]E, not peer-reviewed.
  • Whether long-term use is safe: there are no human data for any of them [25]regulator [38]E, not peer-reviewed.
  • What MOTS-c does in humans: results of the first trial are expected in 2027 at the earliest [35]E, not peer-reviewed.
  • What a product sold online contains: the content has not been tested independently in the sources of this guide.

Other comparisons and substance pages

Another comparison guide covers two peptides sold for recovery. The MOTS-c page has all the sources and user accounts.

Read more: BPC-157 vs TB-500: what is the difference? | AICAR (acadesine) | SLU-PP-332 | MOTS-c | MOTS-c user experiences | SS-31 (elamipretide), another peptide aimed at mitochondria | What are peptides? | Peptides A-Z | NAD+, a coenzyme of cell energy metabolism | NMN, a precursor of NAD+ | Glossary | All guides | Who wrote this: the editors | About us and how we work | AI disclosure: how drafts are checked

FAQ

What is an exercise mimetic?

A substance that makes muscle respond as if it had trained. The idea became known from a 2008 mouse study in which AICAR increased the running endurance of sedentary mice [1]C.

Do AICAR, SLU-PP-332 or MOTS-c work in humans?

It is not known. None has been studied in humans as an exercise mimetic [38]E, not peer-reviewed. The findings are from mice [1, 11, 20]C. The first human trial of MOTS-c is under way [35]E, not peer-reviewed.

Which is more effective, AICAR or SLU-PP-332?

It cannot be said. They have not been compared in the same study, and the methods of the mouse studies differed [1, 11]C.

Is SLU-PP-332 a peptide?

No. It is a small synthetic molecule that activates ERR receptors [11]C [18]D. MOTS-c is a peptide [19]C.

Are exercise mimetics doping?

AICAR, MOTS-c and GW501516 are named in WADA class S4.4.1, which is banned at all times [31]regulator. SLU-PP-332 and SLU-PP-915 are added by name to the 2027 list [32]regulator.

Are they legal in Finland?

AICAR, SLU-PP-332 and MOTS-c are not in the Fimea list of medicines; GW-501516 is in annex 1 A [33]regulator. None has a marketing authorisation in the EU [34]regulator. More: Peptides and the law in Finland. This is not legal advice.

Why is cardarine (GW501516) mentioned?

It is a cautionary example: in mice it improved running capacity together with training [1]C, but its development was stopped for safety reasons [27], and in mice exposed to a cancer-causing substance it led to rapidly spreading stomach cancers [28]C.

What do users report?

User accounts of MOTS-c and SLU-PP-332 have been collected: MOTS-c user experiences and SLU-PP-332 user experiences (user reports, not research). For AICAR too few public accounts were found for a summary.

Sources

  1. Narkar VA, Downes M, Yu RT, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134(3):405-415. PMID 18674809
  2. Cuthbertson DJ, Babraj JA, Mustard KJ, et al. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 2007;56(8):2078-2084. PMID 17513706
  3. Babraj JA, Mustard K, Sutherland C, et al. Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status. Am J Physiol Endocrinol Metab. 2009;296(5):E1042-E1048. PMID 19190259
  4. Boon H, Bosselaar M, Praet SF, et al. Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia. 2008;51(10):1893-1900. PMID 18709353
  5. Bosselaar M, Smits P, van Loon LJ, et al. Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect. J Clin Pharmacol. 2011;51(10):1449-1458. PMID 21148051
  6. Mangano DT. 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
  7. Newman MF, Ferguson TB, White JA, et al. Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. JAMA. 2012;308(2):157-164. PMID 22782417
  8. Wilcox SH, Calixto J, Dray SD, et al. Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression. FASEB Bioadv. 2025;7(3):e1491. PMID 40060947
  9. Guerrieri D, van Praag H. Exercise-mimetic AICAR transiently benefits brain function. Oncotarget. 2015;6(21):18293-18313. PMID 26286955
  10. Van Den Neste E, Van den Berghe G, Bontemps F. AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic malignancies. Expert Opin Investig Drugs. 2010;19(4):571-578. Review. PMID 20367195
  11. Billon C, Sitaula S, Banerjee S, et al. Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chem Biol. 2023;18(4):756-771. Competing interests: stockholders in Myonid Therapeutics. PMID 36988910
  12. Billon C, Schoepke E, Avdagic A, et al. A Synthetic ERR Agonist Alleviates Metabolic Syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. PMID 37739806
  13. Xu W, Billon C, Li H, et al. Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation. 2024;149(3):227-250. PMID 37961903
  14. Wang XX, Myakala K, Libby AE, et al. Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. Am J Pathol. 2023;193(12):1969-1987. PMID 37717940
  15. Bonanni R, Falvino A, Matticari A, et al. Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Front Physiol. 2025;16:1616693. PMID 40692696
  16. Billon C, Appourchaux K, Côté I, et al. An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. J Pharmacol Exp Ther. 2026;393(1):103787. PMID 41421047
  17. Möller T, Krug O, Thevis M. In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. Rapid Commun Mass Spectrom. 2026;40(8):e70039. PMID 41588687
  18. Avliyakulov NK, Sobolevsky T, Ahrens E. Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes. Drug Test Anal. 2026;18(3):439-450. PMID 41688415
  19. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID 25738459
  20. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. PMID 33473109
  21. von Walden F, Fernandez-Gonzalo R, Norrbom J, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol. 2021;131(3):1035-1042. PMID 34351816
  22. Gudiksen A, Hansen CC, van der Stede T, et al. MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner. Free Radic Biol Med. 2026;246:682-696. PMID 41520850
  23. Xing L, Lu B, Zhu X, et al. Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells. Inflamm Regen. 2026;46. PMID 42324588
  24. Kong BS, Lee H, L'Yi S, et al. Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes. Exp Mol Med. 2025;57(8):1861-1877. PMID 40855115
  25. FDA. Briefing document, Pharmacy Compounding Advisory Committee, 23-24 July 2026: MOTS-c-related bulk drug substances (MOTS-c free base and MOTS-c acetate). Read 15 Oct 2026. fda.gov (PDF)
  26. Olson EJ, Pearce GL, Jones NP, Sprecher DL. Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol. 2012;32(9):2289-2294. PMID 22814748
  27. Sahebkar A, Chew GT, Watts GF. New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert Opin Pharmacother. 2014;15(4):493-503. Review. PMID 24428677
  28. Pollock CB, Rodriguez O, Martin PL, et al. Induction of metastatic gastric cancer by peroxisome proliferator-activated receptorδ activation. PPAR Res. 2010;2010:571783. PMID 21318167
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  30. Plaza-Florido A, Lindholm ME, Carrera-Bastos P, et al. Exercise pills for cardiometabolic health cannot mimic the exercise milieu. Trends Endocrinol Metab. 2026;37(4):356-370. Review. PMID 40784868
  31. WADA. World Anti-Doping Code International Standard: Prohibited List 2026, classes S0 and S4.4.1. wada-ama.org (PDF)
  32. WADA. Prohibited List 2027 (tracked-changes version, 26 Aug 2026; approved 10 Sep 2026, in force 1 Jan 2027), class S4.4.1. wada-ama.org (PDF)
  33. Finnish Medicines Agency (Fimea). Decision on the list of medicines 230/2025, annexes 1 and 1 A (in force from 19 May 2025), in Finnish. Read 15 Oct 2026. Finlex
  34. European Medicines Agency. Medicines data (centrally authorised medicines, data set of 14 Oct 2026): no medicine with AICAR (acadesine), SLU-PP-332, MOTS-c or GW501516 as active substance. EMA
  35. ClinicalTrials.gov. NCT07505745: MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity (Hudson Biotech; phase 2; placebo-controlled; subcutaneous injection once daily for 12 weeks; recruiting as of 15 Oct 2026; primary completion estimated Feb 2027). ClinicalTrials.gov not peer-reviewed
  36. ClinicalTrials.gov. NCT03998514: A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (CohBar; phase 1; completed; no results posted as of 15 Oct 2026). ClinicalTrials.gov not peer-reviewed
  37. CohBar, Inc. Annual report (Form 10-K) for 2020, filed 30 Mar 2021: CB4211 described as "a novel, enhanced analog of MOTS-c". Read 15 Oct 2026. sec.gov not peer-reviewed
  38. ClinicalTrials.gov, registered trials by intervention as of 15 Oct 2026: AICAR 2 (NCT00168519, NCT00004314), acadesine 3 (NCT00559624 leukaemia, NCT01813838, NCT00872001 heart surgery, phase 3, terminated), SLU-PP-332 0, SLU-PP-915 0, MOTS-c 1 as intervention (NCT07505745), CB4211 1, GW501516 3 (started 2003-2004). None tests a substance as an exercise mimetic. ClinicalTrials.gov not peer-reviewed
  39. de Souza-Lima J, Astrosa-Martin BD, Galaz-Rodríguez CA, et al. Pharmacological Activation of ERRα/β/γ as an Exercise Mimetic: Potential Therapeutic Applications. Rev Med Chil. 2026;154(2):237-245. Systematic review (in Spanish, English abstract). PMID 42024694

PubMed details checked on 15 Oct 2026. FDA, Finlex, EMA, SEC and ClinicalTrials.gov pages read on 15 Oct 2026. Sources 35-38 are not peer reviewed. This page has no seller or affiliate links.

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