MOTS-c: what the research shows, and what it doesn't

MOTS-c is one of four peptides an FDA advisory committee reviewed on July 23, 2026. The research on it is limited: one discovery paper from 2015, some cell and mouse studies, and a few studies that measured it in human blood. Each kind of study supports different conclusions, and what is missing matters as much as what was found.

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, first reported in 2015 from cell and mouse experiments. Human studies so far measure its blood levels and show associations only, and the one registered drug trial has posted no findings. FDA staff proposed not adding it to the 503A bulks list.

For laboratory research use only. Not for human or veterinary use. Nothing here is medical advice.

What MOTS-c is

The name stands for "mitochondrial open reading frame of the 12S rRNA-c." The 2015 paper that named it reports "a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c."[2] The paper defines a sORF as a short open reading frame, here one in mitochondrial DNA, the small genome mitochondria carry apart from the cell nucleus.

The FDA's 2026 briefing document gives the sequence as H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH (one-letter code MRWQEMGYIFYPRKLR). It lists the free base's molecular formula as C101H152N28O22S2, its molecular weight as 2174.6 g/mol, and its CAS number as 1627580-64-6.[1] At 16 amino acids it is a little longer than BPC-157, which has 15. FDA's safety-risks page spells the name "MOTs-C."[3]

The 2015 discovery paper (cells and mice)

Lee and colleagues described MOTS-c in Cell Metab on March 3, 2015.[2] Model: cell culture and mouse. The abstract describes experiments in aged mice and in mice fed a high-fat diet, along with cell work on the folate cycle and AMPK.[2] We read the abstract, not the full text, so the study parameters and the size of each effect are not summarized here.

The FDA's own review of the preclinical work is cautious. It says those studies "were limited to in-vitro and in-vivo rodent models," that "assessments of the dose-response relationships for the effects of MOTS-c are missing," and that "the molecular targets through which MOTS-c acts remain unknown."[1]

Human studies: blood levels, not a drug

The human studies we found measure the MOTS-c already present in people's blood. None of them gave MOTS-c to anyone. Model: human, observational.

• Du et al., 2018 (Pediatric Diabetes), a case-control study in Hubei Province, China, of 40 children and adolescents with obesity and 57 controls, reported that "MOTS-c levels were significantly decreased in the obese group compared with the control group."[5]
• Ramanjaneya et al., 2019 (Frontiers in Endocrinology), a cross-sectional study of serum from 225 people in Qatar, reported that "serum MOTS-c was significantly lower in T2D subjects compared to controls." The same abstract reports that circulating MOTS-c correlated positively with BMI.[6]

A study like these can show that two measurements move together. It cannot show that one causes the other, or which way any link runs. The two also point in different directions on body size: one found lower levels in children with obesity, the other a positive correlation with BMI in adults.[5][6]

The registered trial

ClinicalTrials.gov lists one interventional study that gives MOTS-c to people: NCT07505745, a phase 2a, randomized, double-blind, placebo-controlled study in adults with prediabetes and overweight or obesity. The sponsor is Hudson Biotech, a company. The record lists the status as recruiting (verified March 2026), an actual start date of February 2, 2026, an estimated primary completion date of February 14, 2027, an estimated enrollment of 120 and subcutaneous administration.[7] A registry entry describes a plan. No findings have been posted. Two other records measure MOTS-c only as a blood marker.[7]

FDA status, step by step

Scroll sideways to see all of it.

Category 2 and withdrawal. Category 2 is FDA's interim list of bulk substances that may present significant safety risks in compounding. FDA's live page describes its newer table as substances "previously in category 2" that "were withdrawn by the nominators." Its note on MOTs-C stays attached: compounded drugs containing it "may pose significant risk for immunogenicity for certain routes of administration."[3]

The briefing. The nomination came from Wells Pharmacy Network. FDA writes: "The nomination was withdrawn, and FDA is evaluating the substances at its discretion." On human data it states: "No published studies were found in which non-compounded or compounded drug products containing MOTS-c (free base) or MOTS-c acetate were used in humans." It concludes, "we propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List."[1] That is FDA staff's proposal to the committee, not a final decision.

The vote. FDA has posted no minutes, transcript or vote tally for the meeting.[9] The FDA Law Blog reported that "MOTS-c cleared by a narrower 7-5-2 margin," and McDermott Will & Schulte reported that the committee recommended MOTs-c in free base and acetate forms.[10][11] FDA's meeting page says advisory committees make "non-binding recommendations."[9] As of October 13, 2026, these remain reported counts, and no rule has followed.[12]

What the research does not show

• Any finding in people who were given it. FDA found no published human use, and the registered trial has posted none.[1][7]
• That mouse findings carry over. The discovery work was in cells and mice.[2]
• Cause from blood levels. The human studies are observational, and they disagree in direction.[5][6]
• How it acts. FDA's briefing says the molecular targets are unknown and dose-response data are missing.[1]
• A regulatory answer. A committee vote is advice to FDA. It is not approval and not a rule.[9]

Questions people ask

Is MOTS-c a peptide?

Yes. It is a chain of 16 amino acids, MRWQEMGYIFYPRKLR in one-letter code, according to FDA's 2026 briefing document.[1] By contrast, NAD+ is not a peptide.

Where is MOTS-c encoded?

In mitochondrial DNA, within the region for the 12S ribosomal RNA, according to the 2015 discovery paper.[2]

Has MOTS-c been studied in a clinical trial?

One phase 2a trial, NCT07505745, was recruiting when its record was last verified in March 2026. It has posted no findings.[7] FDA's May 2026 briefing found no clinical studies or human exposure data.[1]

Is MOTS-c FDA-approved?

No. FDA staff proposed not adding it to the 503A bulks list, and as of October 13, 2026 no rule had been published.[1][12]

What did the July 2026 committee vote decide?

A reported 7-5-2 vote recommended listing it. The vote is advisory, FDA has posted no record of it, and the agency has not acted on it.[9][10] Our page on the FDA compounding process explains how lists, categories and votes differ.

For laboratory research use only. Not for human or veterinary use, diagnostic, or therapeutic purposes.

Sources (fetched October 13, 2026)

1. FDA briefing document, Pharmacy Compounding Advisory Committee, MOTS-c-related bulk drug substances (dated 5/11/2026): https://www.fda.gov/media/193347/download
2. Lee C, Zeng J, Drew BG, et al., Cell Metab 2015;21(3):443-54 (March 3, 2015). PMID 25738459, abstract: https://pubmed.ncbi.nlm.nih.gov/25738459/
3. FDA, "Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks" (content current as of 04/22/2026): https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
4. Internet Archive copy of source 3, captured March 5, 2026: https://web.archive.org/web/20260305132226/https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
5. Du C et al., Pediatric Diabetes, 2018. PMID 29691953, abstract: https://pubmed.ncbi.nlm.nih.gov/29691953/
6. Ramanjaneya M et al., "Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects," Frontiers in Endocrinology, 2019;10:331. PMID 31214116, abstract: https://pubmed.ncbi.nlm.nih.gov/31214116/
7. ClinicalTrials.gov, NCT07505745: https://clinicaltrials.gov/study/NCT07505745 ; biomarker records NCT07678073 and NCT04027712: https://clinicaltrials.gov/study/NCT07678073 ; https://clinicaltrials.gov/study/NCT04027712
8. Federal Register, Pharmacy Compounding Advisory Committee notice of meeting, FR Doc. 2026-07361, April 16, 2026: https://www.federalregister.gov/documents/2026/04/16/2026-07361/pharmacy-compounding-advisory-committee-notice-of-meeting-establishment-of-a-public-docket-request
9. FDA, July 23-24, 2026 PCAC meeting page (content current as of 08/06/2026): https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026
10. Hyman, Phelps & McNamara, FDA Law Blog, "PEPTIDE-L WAVE! PCAC Approves Four Bulk Drug Substances for the 503A List," July 24, 2026: https://www.thefdalawblog.com/2026/07/peptide-l-wave-pcac-approves-four-bulk-drug-substances-for-the-503a-list/
11. McDermott Will & Schulte, "Bulk-list bound? PCAC backs majority of peptides in two-day public meeting," July 27, 2026: https://www.mcdermottlaw.com/insights/bulk-list-bound-pcac-backs-majority-of-peptides-in-two-day-public-meeting/
12. Federal Register search, "MOTS-c," October 13, 2026: https://www.federalregister.gov/documents/search?conditions%5Bterm%5D=%22MOTS-c%22