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Therapeutics

MOTS-c

MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region. In rodent studies it activates AMPK, inhibits the folate-purine cycle, and improves insulin sensitivity, glucose homeostasis, and exercise capacity; circulating MOTS-c rises transiently with exercise, which is the basis for the popular "exercise mimetic" framing. Human data are limited to small observational studies of endogenous levels. MOTS-c is not approved as a medicinal product by the FDA, EMA, PMDA, or NMPA as of 2026. The FDA added MOTS-c to the 503A Category 2 bulk-substance list in 2023 (peptides flagged as raising significant safety risks for compounding), then removed it on 22 April 2026 alongside 11 other peptides whose nominators withdrew, with formal PCAC review scheduled for July 2026; outside that pending review it still circulates only as a research-use peptide.

Sources

  1. Lee C, Zeng J, Drew BG, et al.. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. *Cell Metabolism*doi:10.1016/j.cmet.2015.02.009
  2. Reynolds JC, Lai RW, Woodhead JST, et al.. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. *Nature Communications*doi:10.1038/s41467-020-20790-0
  3. U.S. Food and Drug Administration. (2023). Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (503A Category 2 list, peptide additions)