Mitochondrial

MOTS-c

US status
PCAC-recommended · pending
Class
Mitochondrial
Approved product
None
Route
None lawful; sold as research-use-only material

By Peptide America · Publisher · Reviewed August 2026

Regulatory record

3 dated actions on record; no FDA final action yet.
April 2026
Removed from Category 2 without Category 1 listing.
July 2026
PCAC votes 7–5 (two abstentions) to recommend 503A listing; advisory only. FDA has published no minutes, transcript or vote summary for this meeting; the tally is as reported by McDermott Will & Schulte and LumaLex Law.
FDA final action
None as of August 2026.

Every entry above is dated; the record is current as of the review date.

Definition

MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome, one of a small family of mitochondrial-derived peptides described over the past decade; it acts as a metabolic signaling molecule rather than a structural protein.

Interest in the compound comes from exercise physiology and metabolism, where it is studied as a messenger linking mitochondrial state to whole-body insulin sensitivity.

Evidence

The foundational work is preclinical: the 2015 discovery paper showed MOTS-c promoting metabolic homeostasis and reducing diet-induced obesity and insulin resistance in mice [1]. Human data remain early and largely observational; no efficacy trial supports a clinical use.

The compound is marketed to athletes and biohackers well ahead of that record; the marketing claims run years in front of any human data.

Lawful access

MOTS-c was removed from Category 2 of the interim 503A bulks list in April 2026 without Category 1 listing, and in July 2026 the Pharmacy Compounding Advisory Committee voted to recommend adding it to the section 503A list. The margin is reported as 7–5 with two abstentions by McDermott Will & Schulte and by LumaLex Law, whose separate accounts of the meeting agree substance by substance [2, 3]; the FDA has published no minutes, transcript or vote summary, so the figure is secondary and this page says so wherever it appears. The vote is advisory; no FDA final rule has issued, and no licensed pharmacy may lawfully compound MOTS-c as of August 2026.

Material sold online today is research-use-only supply, outside pharmacy oversight.

Supply

No lawful US supply route exists for this molecule today. Lawfully available alternatives are recorded in the molecule index; the regulatory record on this page tracks the rulemaking that could change this.

Elsewhere in this index

Filed under

Evidence reviews

Reference tables

Same class

References

  1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443–454. PMID 25738459
  2. McDermott Will & Schulte. Bulk-list bound? PCAC backs majority of peptides in two-day public meeting. July 27, 2026. Read August 2026. A secondary account, cited because the FDA has published no minutes, transcript or vote summary for the July 23–24, 2026 meeting; the agency's meeting page, content current as of August 6, 2026 and re-read in August 2026, carries the briefing documents, the final agenda, the final meeting roster and the FDA presentations, and no record of any vote. This report gives the tally for each substance and states that FDA scientists recommended against inclusion in each instance. Source
  3. LumaLex Law. The July 2026 PCAC Peptide Meeting. July 25, 2026. Read August 2026. A second, independent secondary account, checked against the first: it prints all seven July 23–24, 2026 votes as a table — BPC-157, KPV and TB-500 at 8–6–1, MOTS-c at 7–5–2, Semax at 8–5–1, Epitalon at 7–4–1, and emideltide (DSIP) at 6–7–1 — and the two accounts agree substance by substance. Source
  4. PubMed, National Library of Medicine. Census run September 2026 across three name variants — "MOTS-c" OR "MOTS-C peptide" OR "mitochondrial open reading frame of the twelve S rRNA type-c" — returning 254 indexed records, 143 carrying the Humans MeSH term, 5 under "clinical trial"[Publication Type] and 4 under "randomized controlled trial"[Publication Type]; 92 records carry the mice or rats MeSH terms, and 25 carry both the term exercise and the Humans term. All five trial-type records were opened and read, and not one administers the peptide: a 2020 multicenter study using circulating MOTS-c as a predictor of outcome in diabetic patients with coronary disease, a 2021 study of circulating MOTS-c after a single bout of endurance or resistance exercise, a 2021 study of circulating MOTS-c after a 16-week exercise program in breast cancer survivors, a 2022 study of circulating MOTS-c in breast cancer patients randomized to metformin that found no significant change, and a 2025 study of circulating MOTS-c after repeated heat exposure during limb immobilization. The publication-type filter was proved live in the same run against a control term returning 8,906 records under the clinical-trial type and 6,115 under the randomized type; the invalid tag clinicaltrial[pt] returned 0 for that control term, and a deliberately invalid record identifier errored at the start and the end of the run. The counts reproduce the August 2026 run behind the trial-record table exactly. Source
  5. von Walden F, Fernandez-Gonzalo R, Norrbom J, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021;131(3):1035–1042. PMID 34351816
  6. Dieli-Conwright CM, Sami N, Norris MK, et al. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep. 2021;11(1):16916. PMID 34413391
  7. Elhusseiny R, Ihsan M, Labidi M, et al. Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization. Med Sci Sports Exerc. 2025;57(12):2764–2774. PMID 40674654
  8. US Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks, content current as of April 22, 2026, table of bulk drug substances nominated but withdrawn, entry for MOTs-C (the page's spelling). Read September 2026. The entry states that compounded drugs containing the substance may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization, that FDA has not identified any human exposure data on drug products containing it administered via any route of administration, and that FDA lacks important information regarding any safety issues it raises, including whether it would cause harm if administered to humans. Source
  9. US Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, updated May 14, 2026. Read in full September 2026: "MOTS" occurs nowhere in the document, so the substance appears in none of Category 1, Category 2, or Category 3. Control in the same read: the same document names GHK-Cu six times. Source
  10. US Food and Drug Administration, Drugs@FDA through the openFDA drugsfda endpoint. Queried September 2026 on the generic name, the substance name and the brand name for "MOTS-c": no matching application. Control in the same run: the identical query for "bremelanotide" returned NDA 210557. Source