Compounds / MOTS-c
MOTS-c
Also known as: MOTS-c; Mitochondrial ORF of the 12S rRNA type-c; mitochondrial-derived peptide; MOTS-c acetate
Primary research focus: Metabolic and mitochondrial research (insulin sensitivity, exercise mimetic, aging biology)
Last updated July 2026 · Reviewed against FDA labeling and published research.
What is MOTS-c?
MOTS-c is a 16-amino-acid peptide encoded not by nuclear DNA but by the mitochondrial genome itself (the MT-RNR1 / 12S rRNA region), making it one of the first identified mitochondrial-derived peptides. Discovered in 2015 at USC, it is studied as an exercise mimetic and metabolic regulator: levels rise with exercise and decline with age. It is not FDA-approved, its human evidence is sparse, and its US compounding eligibility is being decided at an FDA advisory committee meeting on July 23, 2026.
MOTS-c is translated in the cytoplasm from a mitochondrially encoded short open reading frame. Under metabolic stress it translocates to the nucleus, where it acts as a mitochondrial-to-nuclear signal regulating expression of nuclear genes involved in metabolism and stress adaptation. Its most cited mechanism is activation of AMPK, the cellular energy sensor, with downstream effects on glucose uptake in skeletal muscle, fatty acid oxidation, and the folate-methionine cycle (via AICAR accumulation). It has also been reported to bind casein kinase 2. This mechanistic picture comes from animal and cell studies; it is not confirmed in humans.
How it’s supplied
Not an FDA-approved or commercially manufactured medicine. It is sold as a research-grade lyophilized peptide for reconstitution, and has been dispensed by compounding pharmacies during periods when that was permitted. Research-grade products are not FDA-reviewed for potency or sterility; because the peptide is short, truncated or oxidized variants can be hard to distinguish without mass-spectrometry confirmation.
Dosage Chart
Units shown are for a U-100 insulin syringe (100 units = 1 mL), calculated from the vial size and BAC water you select. Always confirm against your prescription and your syringe markings.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Weeks 1-4 | 0.5mg | 1x Daily | — |
| Weeks 5-8 | 1mg | 1x Daily | — |
- Rotate injection sites to reduce irritation and lipohypertrophy
- Not for use during pregnancy or breastfeeding
- Do not exceed the recommended dose to try to speed results
Potential Benefits and Side Effects
Effects reported in published research. Not a promise of results, and not medical advice.
- Reported in preclinical (mouse and cell) research and cross-sectional human data; human efficacy is not established.
- Improved insulin sensitivity and glucose metabolism in skeletal muscle in animal models.
- Reduced obesity and improved metabolic homeostasis in diet-induced obese mice.
- AMPK activation, reproducing aspects of the metabolic response to exercise (exercise-mimetic framing).
- Reported effects on muscle atrophy, bone metabolism, and inflammation in preclinical models.
- No robust human adverse-effect data are available for native MOTS-c.
- Preclinical studies have not reported overt toxicity, but human tolerability and long-term safety are uncharacterized.
- Research-grade material carries identity, purity, and oxidation risks.
Warnings and contraindications
Important safety information. This is not exhaustive — read the full prescribing information and consult your prescriber or pharmacist.
- No FDA-approved labeling exists; the following reflect the compound's status and the limits of its evidence, not established label warnings.
- Human clinical evidence is sparse: no completed Phase 2 or Phase 3 trial of native MOTS-c exists, and the only completed controlled trial used CB4211, an analog rather than MOTS-c itself.
- Ahead of the July 23, 2026 advisory committee meeting, the FDA proposed that MOTS-c not be added to the 503A bulks list, citing insufficient effectiveness and safety evidence; legal access through compounding may end.
- MOTS-c is explicitly named on the 2026 WADA Prohibited List under section S4.4.1 (AMPK activators) and is prohibited at all times.
- Research-grade material varies in identity and purity; a +16 Da oxidation adduct (methionine sulfoxide) is a known quality issue.
- Safety in pregnancy and breastfeeding has not been studied.
- Not established; no FDA-approved labeling. Precautionary considerations include known hypersensitivity and use by athletes subject to anti-doping rules.
Reconstitution Steps
How to prepare the lyophilized vial. Confirm specifics with your pharmacist or prescriber.
- Confirm the amount of peptide in the vial and the volume of diluent you intend to use before starting.
- Wash your hands and gather supplies: the lyophilized vial, the diluent (typically bacteriostatic water), an alcohol swab, and a sterile syringe.
- Let the vial and diluent reach room temperature if they were refrigerated or frozen.
- Wipe the rubber stopper of both the peptide vial and the diluent vial with a fresh alcohol swab and let them air dry.
- Draw the intended diluent volume into the syringe.
- Insert the needle into the vial and slowly release the diluent down the inside wall rather than directly onto the powder, to avoid foaming.
- Do not shake. Gently swirl or roll the vial until fully dissolved.
- Inspect the solution: it should be clear and colorless with no visible particles. Do not use if cloudy or containing particles.
- Note the resulting concentration (amount divided by diluent volume) so it matches the reconstitution calculator on this page.
- Label the vial with the reconstitution date and store as directed under reconstituted storage.
US regulatory status
Classifications are public record but can change. For reference only, not legal advice.
Development: MOTS-c was discovered in 2015 by a team led by Changhan Lee in the Pinchas Cohen laboratory at the USC Davis School of Gerontology, reported in Cell Metabolism, which showed it promotes metabolic homeostasis and reduces obesity and insulin resistance in mice. Subsequent preclinical work spans insulin resistance, obesity, muscle atrophy, bone metabolism, inflammation, and aging biology, with cross-sectional human data showing plasma levels decline with age. Clinical translation has been limited: CohBar developed CB4211, a MOTS-c analog, which completed a controlled trial, but CohBar has since wound down and no active Phase 2 or Phase 3 program for native MOTS-c exists (a Phase 2a prediabetes study has reportedly been registered). MOTS-c (free base and acetate) was removed from FDA Category 2 in the April 2026 update and scheduled for Pharmacy Compounding Advisory Committee review on July 23, 2026 under docket FDA-2025-N-6895, with obesity and osteoporosis as the nominated uses. In its pre-meeting materials the FDA proposed that MOTS-c not be added to the 503A bulks list, finding insufficient effectiveness and safety evidence.
Notes: MOTS-c is not FDA-approved for any indication. Its compounding status is unsettled: it was removed from Category 2 in April 2026 but was not placed in Category 1, leaving it in an interim position pending Pharmacy Compounding Advisory Committee review scheduled for July 23, 2026. Ahead of that meeting the FDA proposed that MOTS-c (free base and acetate) not be added to the 503A bulks list, citing insufficient evidence of effectiveness and safety; the committee vote and final FDA determination will settle the question, so verify against the current FDA list. MOTS-c is prohibited at all times in sport under the 2026 WADA Prohibited List (section S4.4.1, AMPK activators). It is not a controlled substance. (Status current as of mid-2026.)
International status
Pharmacokinetics
Storage and handling
Important Notes
Practical considerations for consistency and safety.
- MOTS-c is encoded by mitochondrial DNA rather than nuclear DNA, which is what makes it unusual among peptides.
- Its compounding status is actively being decided: the FDA has proposed NOT adding it to the 503A bulks list ahead of the July 23, 2026 advisory committee meeting; verify the current classification.
- The only completed controlled human trial used CB4211, an analog, not native MOTS-c.
- It is explicitly named on the 2026 WADA Prohibited List under AMPK activators (S4.4.1).
- Lot-specific mass spectrometry is worth requesting; the +16 Da oxidation adduct indicates methionine sulfoxide formation.
Lifestyle Factors
- Its biology is tied to exercise: endogenous MOTS-c rises with physical activity, and it is often framed as an exercise mimetic rather than an exercise replacement.
- Human lifestyle interactions for the exogenous peptide are not characterized.
References
Related compounds
Important disclaimer
This page is an educational reference, not medical advice, a diagnosis, or a treatment recommendation, and not a substitute for your prescriber or pharmacist. Approval and regulatory status varies by compound and can change. Always confirm against current prescribing information and consult a qualified healthcare professional before making any decision about a medication.