MOTS-c
Mitochondrial ORF of the 12S rRNA type-c
A mitochondrial-derived peptide studied as an exercise mimetic that improves metabolic homeostasis and insulin sensitivity in animal models.
Overview
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that acts as a signaling molecule regulating metabolism. In animal studies it improves insulin sensitivity, protects against diet-induced obesity, and mimics some effects of exercise; early human data are limited. It is investigational and not an approved therapeutic. Regulatory update, September 2026: the FDA removed this peptide from Category 2 of the 503A bulk-drug list in April 2026, and on July 23 to 24, 2026 the Pharmacy Compounding Advisory Committee voted to recommend it for compounding against the advice of FDA scientists, who found no adequate human data. The vote is advisory; nothing changes until FDA rulemaking, and vials sold 'for research' remain unapproved drugs. A Phase 2a trial in prediabetes (NCT07505745) is the first controlled human study of unmodified MOTS-c.
Mechanism of action
Translocates to the nucleus under metabolic stress and activates AMPK-related pathways that regulate glucose and lipid metabolism.
Key studies & citations
- Animal2015
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
Identified MOTS-c as a 16-amino-acid peptide encoded in mitochondrial 12S rRNA; treatment in mice prevented age- and diet-induced insulin resistance and diet-induced obesity via AMPK activation.
Cell Metabolism - Animal2021
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
MOTS-c improved physical performance in young, middle-aged and old mice and, started late in life, increased healthspan; exercise raised endogenous MOTS-c in human muscle and plasma.
Nature Communications - Human2026
A Phase 2a, randomized, double-blind, placebo-controlled study of MOTS-c in adults with prediabetes and overweight/obesity (NCT07505745)
Recruiting Phase 2a trial (sponsor Hudson Biotech, started February 2026) of subcutaneous MOTS-c versus placebo for insulin sensitivity; no results yet.
ClinicalTrials.gov - Review2026
July 23-24, 2026 meeting of the Pharmacy Compounding Advisory Committee
Official record of the meeting at which MOTS-c was considered for the 503A bulks list; the committee's 7 to 5 vote to recommend it went against FDA reviewers' position and is advisory only.
U.S. FDA (Advisory Committee Calendar)
Frequently asked questions
Is MOTS-c proven in humans?
No. The strongest evidence is from animal studies. Human research is early, so it is best considered preliminary.