MOTS-c

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Snapshot

Chemistry and make-up

MOTS-c is a short 16-residue peptide encoded not by the nuclear genome but within the mitochondrial 12S rRNA gene, which is what makes it a “mitochondrial-derived peptide” (MDP). It is linear, has no cysteine (no disulfide bridges) and no metal binding. Chemically the notable features are two methionine residues (positions 1 and 6), which are oxidation-prone, and multiple basic residues (three arginines plus a lysine) that make it fairly water-soluble and positively charged. That methionine content is the main practical QC flag: oxidised MOTS-c shows up as a +16 Da mass shift, so a CoA should report an observed mass and ideally show the peptide is not partly oxidised. Sold mostly as the acetate salt; the counterion and any TFA residue should be stated on the CoA. Verify formula/MW against PubChem CID 146675088 (C101H152N28O22S2, ~2174.6 g/mol), which matches the brief.

What it is studied for (evidence)

• Mechanism (preclinical [A]): MOTS-c is described as an exercise mimetic. It regulates metabolic homeostasis largely through the folate-AICAR-AMPK pathway, activating AMPK, and under metabolic stress it translocates to the nucleus and directly regulates adaptive/antioxidant gene expression. It augments muscle mitochondrial bioenergetics in a PGC-1α / AMPK-dependent manner (ScienceDirect / PubMed 41520850; J Transl Med 2023, PMC9854231) [A].
• Established (in animals): consistent rodent evidence that MOTS-c improves insulin sensitivity in aged and diet-induced-obese mice, regulates glucose and lipid metabolism, and that endogenous MOTS-c is exercise-induced and declines with age. It improved physical capacity and muscle homeostasis in aged mice (Nature Communications 2021; PMC6640593) [A]. This is a genuinely interesting biology story, but it is animal and mechanistic.
• Human clinical status (thin, and mostly an analog): native MOTS-c itself has no completed, published human efficacy trial as of 2026. The furthest-advanced human work is on CB4211, an engineered MOTS-c *analog* by CohBar, which completed a Phase 1a/1b randomised, placebo-controlled study (25 mg SC daily, 4 weeks, 20 obese NAFLD subjects). It met its primary safety/tolerability endpoint with no serious adverse events and reported reductions in ALT/AST versus placebo, but this was a small early-phase study on an analog, not proof of clinical benefit for MOTS-c (CohBar topline, BioSpace) [A/D — small phase 1, analog]. Weight it as “first-in-human feasibility”, not efficacy.
• Marketing claims vs data: vendor and clinic pages routinely present MOTS-c as a proven fat-loss, anti-ageing, or “exercise in a vial” product for humans. The human evidence does not support that. The honest position is: strong and coherent preclinical metabolic biology, essentially no human efficacy data for the native peptide.

Handling, format and stability

Supplied lyophilised; reconstituted with bacteriostatic or sterile water for research handling only (no dosing guidance here). Store lyophilised cold and protected from light; reconstituted peptide is less stable and cold-chain dependent. Because of the two methionines, methionine oxidation is the key stability liability for this peptide, so minimise air/light exposure and expect a fresh, well-handled batch to show minimal +16 Da oxidised species on MS.

Regulatory and trade status

• UK/EU RUO: research use only; not an approved medicine. Keep listings and email language strictly research-use; healing/performance claims risk “medicinal product by presentation”.
• US: not FDA-approved for any indication; not legally marketed for human therapeutic use.
• WADA (sport): PROHIBITED at all times. MOTS-c is an explicitly named substance under S4.4 (Metabolic Modulators), sub-section S4.4.1 (AMPK activators) of the 2026 Prohibited List, alongside AICAR. It is a non-Specified Substance, which carries the standard (higher) sanction range. Athletes under testing should treat it as banned in and out of competition (WADA 2026 Prohibited List; USADA explainer) [B]. This is an important customer-facing flag for any sport-adjacent buyer.
• Customs: peptide-class research chemical; identity/salt clarity is the main trade risk.

Sources

• [A] MOTS-c improves muscle mitochondrial bioenergetics (PGC-1α/AMPK), PubMed 41520850 — https://pubmed.ncbi.nlm.nih.gov/41520850/
• [A] MOTS-c: effects and mechanisms in stress, metabolism, aging, *J Transl Med* 2023 (PMC9854231) — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854231/
• [A] MOTS-c exercise-induced regulator of physical decline, *Nat Commun* 2021 — https://www.nature.com/articles/s41467-020-20790-0
• [A] MOTS-c regulates plasma metabolites / insulin sensitivity (PMC6640593) — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640593/
• [A] MOTS-c in human aging and age-related disease review (PMC9570330) — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570330/
• [A/D] CohBar CB4211 (MOTS-c analog) Phase 1a/1b topline — https://www.biospace.com/cohbar-announces-positive-topline-results-from-the-phase-1a-1b-study-of-cb4211-under-development-for-nash-and-obesity
• [B] USADA — what is the MOTS-c peptide — https://www.usada.org/spirit-of-sport/what-is-mots-c-peptide/
• [B] WADA Prohibited List — https://www.wada-ama.org/en/prohibited-list
• [B] PubChem CID 146675088
• [D] Vendor/clinic pages (superpower.com, pepdex, peptidemark) — commercial; publish dosing, which we do not use.

Plain summary

MOTS-c is a 16-amino-acid peptide encoded inside mitochondrial DNA that acts like an “exercise mimetic” through the AMPK energy-sensing pathway, with a strong and consistent story in mice for insulin sensitivity, metabolism and ageing. Human evidence is thin: the native peptide has no completed efficacy trial, and only an engineered analog (CB4211) reached an early safety study, so treat fat-loss and anti-ageing claims as unproven. Note for any sport customer that MOTS-c is banned by WADA at all times as an AMPK-activating metabolic modulator.

For laboratory and research use only (RUO). Not for human or veterinary use, not for consumption, and not a medicine. Information is a research summary, not medical advice, and contains no dosing guidance.

For laboratory research use only. Not for human or veterinary use, not for consumption, and not a medicine. This is a research summary, not medical advice, and contains no dosing guidance.