MOTS-c
Mitochondrial-derived peptide (research peptide)
Status
Not approved
Not approved anywhere; FDA removed it from its Category 2 compounding safety-risk list in April 2026 after the nomination was withdrawn, and in July 2026 an FDA advisory committee voted 7-5 (two abstentions) to recommend adding it to the 503A bulks list for obesity and osteoporosis, a non-binding vote that awaits FDA action.
Evidence
Animal data only
Effects on insulin sensitivity, obesity and physical capacity come from mouse and cell studies; the first placebo-controlled human efficacy trial began in 2026.
In sport
WADAProhibited (WADA)
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that, in mice, acts as an exercise-like metabolic signal improving insulin sensitivity. It is unapproved and sold as a research peptide; the first placebo-controlled human efficacy trial began in 2026.
Structure
16 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
H-M-R-W-Q-E-M-G-Y-I-F-Y-P-R-K-L-R-OH
What it is used for
- Insulin resistance and prediabetes (studied)
- Obesity (studied)
- Exercise capacity and age-related physical decline (claimed, unproven)
- Osteoporosis (claimed, unproven)
How it works
MOTS-c is encoded within the mitochondrial 12S rRNA gene. In mice it acts mainly on skeletal muscle, inhibiting the folate cycle and de novo purine synthesis, which builds up the metabolite AICAR and activates AMPK, the cell's energy sensor. Under metabolic stress it can move into the nucleus and regulate genes with antioxidant response elements. In humans, exercise raises MOTS-c in muscle and blood. Whether giving it as a drug reproduces these effects in people is unknown.
How strong the evidence is
Animal data only
The discovery study (Cell Metabolism 2015) found that MOTS-c treatment prevented diet-induced obesity and age- and diet-related insulin resistance in mice. A 2021 Nature Communications study showed exercise raises MOTS-c in human muscle and plasma and that late-life treatment improved physical capacity in old mice. A MOTS-c analog (CB4211) completed a phase 1a/1b trial, and a 120-person phase 2a placebo-controlled trial of MOTS-c in prediabetes with overweight began in China in February 2026 (NCT07505745). No human efficacy results are published.
Risks and side effects
- No published human efficacy or long-term safety data
- FDA flagged possible immunogenicity and a lack of human exposure data
- Sold as a research chemical: products may be mislabeled, under- or overdosed, impure, or contaminated, and are not made to pharmaceutical standards
- Prohibited in sport under WADA S4.4 (AMPK activators)
Regulatory status
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | No authorised medicine | Source 12 |
| EUEuropean Union | No authorised medicine | Source 13 |
| UKUnited Kingdom | No authorised medicine | Source 14 |
| AUAustralia | No authorised medicine | Source 15 |
| CACanada | No authorised medicine | Source 16 |
Timeline
2026
- ResearchMOTS-c protects retinal blood-vessel cells in mouse and laboratory models
- RegulatoryFDA advisers vote to allow compounding of BPC-157, KPV, TB-500 and MOTS-c
- RegulatoryFDA removes BPC-157 and 11 other peptides from its compounding safety-risk list
- SafetyHealth Canada warns against injecting peptides bought online and names seized products
Sources
- 01Mitochondrial-derived peptide MOTS-c (A0A0C5B5G6, MOTSC_HUMAN)(opens the source in a new tab)
- 02The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance(opens the source in a new tab)
- 03The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress(opens the source in a new tab)
- 04MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis(opens the source in a new tab)
- 05Phase 2a trial of MOTS-c in adults with prediabetes and overweight or obesity (NCT07505745)(opens the source in a new tab)
- 06Phase 1a/1b study of CB4211 in healthy subjects and subjects with nonalcoholic fatty liver disease (NCT03998514)(opens the source in a new tab)
- 07Certain bulk drug substances for use in compounding that may present significant safety risks(opens the source in a new tab)
- 08July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee(opens the source in a new tab)
- 09FDA panel votes to loosen restrictions for four peptides(opens the source in a new tab)
- 10FDA to remove 12 popular peptides from the Category 2 list(opens the source in a new tab)
- 11World Anti-Doping Code International Standard: Prohibited List 2026(opens the source in a new tab)
- 12FDA Briefing Document: MOTS-c-Related Bulk Drug Substances, Pharmacy Compounding Advisory Committee(opens the source in a new tab)
- 13Find medicine: centrally authorised medicines(opens the source in a new tab)
- 14MHRA Products: active substances beginning with M(opens the source in a new tab)
- 15Australian Register of Therapeutic Goods (ARTG)(opens the source in a new tab)
- 16Think twice before injecting peptides bought online: unauthorized products can seriously harm you(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.