Skip to content

Reference information only. Therapept does not sell peptides and does not provide medical advice.Research-use notice

Therapept

16-residue peptide encoded by a short open reading frame in mitochondrial 12S rRNA

MOTS-c — evidence

What has been published, classified by the kind of document it is. This is not a protocol, not a score, and not a recommendation for use.

Evidence overview

3 records in this file

  • ANIMAL1
  • REGULATORY2

Research areas. Metabolic models; United States compounding.

Publication span. 2015–2026.

What we know

  • Lee et al. 2015 (Cell Metabolism) is the originating characterisation of MOTS-c in mouse metabolic models.
  • No FDA-approved product exists. FDA's withdrawn-nominations table states that human exposure data have not been identified.
  • PCAC discussed MOTS-c-related bulk substances on 23 July 2026. FDA briefing materials proposed against inclusion. That is not a listing decision.

Editorial reading of the records below, labelled as Therapept analysis. How records are built

What remains uncertain

  • Human interventional data on MOTS-c itself. CB4211 is a related analogue and is not this compound.
  • Which PubChem representation a given certificate uses.

Regulatory notes

No FDA-approved product

  • No approved drug product exists in Drugs@FDA.
  • Listed on FDA's table of bulk substances nominated for compounding and subsequently withdrawn. FDA states it has not identified human exposure data.
  • On 23 July 2026 PCAC discussed MOTS-c (free base) and MOTS-c acetate (uses evaluated: obesity and osteoporosis). FDA briefing materials proposed that they NOT be included on the 503A Bulks List. Nominations had been withdrawn; FDA elected to proceed. Committee recommendations are non-binding; FDA has not published a listing decision as of this review.

Regulatory status describes how a substance is classified. It is not a safety assessment of any particular material.

Studies and documents

  1. REGULATORY2026FDA compounding classification

    FDA — bulk substances nominated for compounding and withdrawn: MOTS-c

    U.S. Food and Drug AdministrationFDA compounding communications

    Objective
    To record FDA's published compounding position on MOTS-c.
    Endpoint investigated
    Compounding classification

    MOTS-c (styled MOTs-C on the table) appears on FDA's withdrawn-nominations table. Published concerns include immunogenicity risk, peptide-related impurities and API characterisation. FDA states it has not identified human exposure data.

    Limitations. Withdrawn nomination; not a clinical trial review.

    FDA — Certain bulk drug substances for use in compounding may present significant safety risksReviewed 12 September 2026

  2. REGULATORY2026FDA advisory-committee briefing

    FDA PCAC briefing — MOTS-c-related bulk drug substances (23 July 2026)

    U.S. Food and Drug AdministrationFDA PCAC briefing

    Objective
    To record FDA staff's published proposal on 503A Bulks List inclusion for MOTS-c.
    Endpoint investigated
    Proposed compounding-list classification

    PCAC discussed MOTS-c (free base) and MOTS-c acetate on 23 July 2026 (uses evaluated: obesity and osteoporosis). The briefing-document introduction states that FDA is proposing that both NOT be included on the 503A Bulks List. Nominations had been withdrawn; FDA elected to proceed.

    Limitations. Staff proposal and committee advice are non-binding. FDA has not published a listing decision as of this review.

    FDA — PCAC briefing for MOTS-c-related bulk drug substancesReviewed 12 September 2026

  3. ANIMAL2015In vivo (mouse) with supporting cellular work

    The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance

    Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen PCell Metabolism

    Population
    Mice, including diet-induced obesity models
    Objective
    To characterise MOTS-c, a 16-residue peptide encoded by mitochondrial 12S rRNA, in metabolic-homeostasis models.
    Endpoint investigated
    Metabolic-homeostasis measures in mice, including obesity and insulin-resistance models

    Identifies MOTS-c as a mitochondrial ORF-encoded peptide and reports that it promoted metabolic homeostasis and reduced obesity and insulin resistance in the mouse systems tested. This is the originating primary paper for the MOTS-c literature, not a human interventional trial.

    Limitations. Mouse and cellular systems. CB4211 and other analogues are distinct molecules and are not this compound. Findings do not establish human metabolic outcomes.

    DOI 10.1016/j.cmet.2015.02.009Lee et al., Cell Metab (2015)Reviewed 12 September 2026

Last reviewed 12 September 2026 · Compiled by Therapept Editorial · How these records are built