← All compounds · evidence tier first, by design
| Use | E1 | E2 | E3 | E4 | E5 | E6 | E7 | E8 |
|---|---|---|---|---|---|---|---|---|
| E6 Obesity, weight loss and insulin resistance | E6 | |||||||
| E6 Exercise performance, physical capacity and ageing | E6 |
MOTS-c
MRWQEMGYIFYPRKLR
16 residues encoded by a short open reading frame within the mitochondrial 12S rRNA gene (UniProt A0A0C5B5G6).
Also: Mitochondrial open reading frame of the 12S rRNA-c, Mitochondrial-derived peptide MOTS-c
A 16-amino-acid peptide encoded in mitochondrial DNA and found naturally in human blood and muscle. A synthetic version is sold on the gray market with claims of weight loss, better insulin sensitivity, exercise performance and longevity. It is not approved as a medicine in any jurisdiction checked. FDA states it has identified no human exposure data for products containing it by any route. The World Anti-Doping Agency names it as a prohibited metabolic modulator.
- US C gray market
- EU ? not verified
- UK ? not verified
- CA ? not verified
- AU ? not verified
- JP ? not verified
- CN ? not verified
01Regulatory status, by jurisdiction
| Jurisdiction | Status | Detail and primary source |
|---|---|---|
| US | Not approved | Not approved: FDA has approved no product containing MOTS-c. FDA's list of bulk substances that may present significant safety risks places MOTs-C among substances previously in 503A Category 2 whose nominations were withdrawn by the nominators; it is not on the current 503A Category 1 or 2 lists (updated 14 May 2026). FDA cites possible immunogenicity and peptide impurity and characterisation concerns.“FDA has not identified any human exposure data on drug products containing MOTs-C administered via any route of administration.”Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (FDA, content current as of 04/22/2026) · retrieved 2026-10-10 |
| EU UK CA AU JP CN | Not yet verified from a primary source. No status is shown rather than an unsourced one. | |
Sport (WADA): Prohibited · class S4.4.1. “Activators of the AMP-activated protein kinase (AMPK), e.g. 5-N,6-N-bis(2-fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine (BAM15), AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)” WADA source
02What the human evidence shows
Obesity, weight loss and insulin resistance
No human trial of any design has been published for this use.
The founding study reported that MOTS-c treatment in mice prevented diet-induced obesity and age-related and diet-induced insulin resistance. No published human trial of MOTS-c for weight, glucose control or insulin sensitivity was identified. A placebo-controlled phase 2 trial in adults with prediabetes was registered in China in 2026 and is recruiting, with no results. A company-developed analogue (CB4211) completed a phase 1 trial, but that is a different molecule and its results were not identified in a peer-reviewed journal.
- [1] MOTS-c treatment prevented diet-induced obesity and insulin resistance in mice
Registered-study counts: ClinicalTrials.gov intervention search “MOTS-c”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
Exercise performance, physical capacity and ageing
No human trial of any design has been published for this use.
In mice, MOTS-c treatment increased running performance in young, middle-aged and old animals, and treatment started late in life increased physical capacity. In humans, the same study measured only endogenous MOTS-c, which rose in muscle and blood with exercise; no human was given MOTS-c. No human trial of administered MOTS-c for exercise capacity, muscle function or ageing outcomes was identified.
- [2] MOTS-c treatment increased running capacity in young, middle-aged and old mice; endogenous MOTS-c rose with exercise in humans
Registered-study counts: ClinicalTrials.gov intervention search “MOTS-c”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
Key registered trials
| NCT | Title (as registered) | Phase | Status |
|---|---|---|---|
| NCT07505745 | MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity | 2 | Recruiting |
03Safety signals
There are no adequate human safety data. The absence of reported harm is not evidence of safety.
04What is unknown
- No published human data of any kind on administered MOTS-c: no pharmacokinetics, no safety and no efficacy by any route
- Immunogenicity of injected synthetic MOTS-c is unassessed; FDA states compounded MOTS-c may pose significant risk for immunogenicity and raises peptide-impurity and characterisation concerns
- Whether findings in mice on weight, insulin resistance and running capacity apply to humans has not been tested; the first registered human efficacy trial had not reported at review
- Results for the analogue CB4211 were not found in a peer-reviewed journal, and an analogue's effects cannot be assumed for MOTS-c itself
- Regulatory status outside the US was not verified from regulator sources for this record
05Product quality
No independent purity results have been published for this compound yet. The purity programme will publish full methods and vendor-named results, passes and failures, once its protocol has had legal review.
06Citations
- The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance (2015). doi:10.1016/j.cmet.2015.02.009
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis (2021). doi:10.1038/s41467-020-20790-0
Every DOI is resolved against Crossref and every NCT number against ClinicalTrials.gov, title for title, before publication. Regulatory sources are cited inline above with a verbatim quote and retrieval date.
07Mechanism
MOTS-c is a peptide encoded in mitochondrial DNA; in mouse and cell studies it acted mainly on skeletal muscle, inhibiting the folate cycle and de novo purine synthesis and leading to activation of AMP-activated protein kinase (AMPK).
Mechanism is placed last on purpose: a plausible mechanism is not evidence that a compound works in people.
Reviewed by OSMF research team (AI-assisted, source-verified) on 2026-10-10. Found an error? It goes in the corrections log: report it.