MOTS-c

Classification

Mitochondrial-derived peptide (research only)

Approval status

Research only · Not approved for human use

Research status

Endogenous mitochondrial-encoded peptide under investigation. Not an approved drug.

Molecular formula

Insufficient reliable evidence identified.

Molecular weight

Insufficient reliable evidence identified.

Sequence

Mitochondrial ORF-derived 16-amino-acid peptide (MRWQEMGYIFYPRKLR)

Primary biological target

Proposed metabolic / folate-purine / AMPK-related pathways in preclinical work. Mechanism not yet fully established in humans.

Half-life

Insufficient reliable evidence identified for a validated human therapeutic half-life.

Routes investigated

Intraperitoneal (mice), Insufficient standardised human therapeutic route

Human evidence level

D — Primarily animal / preclinical evidence

A research peptide in metabolic and exercise biology. Not an approved medicine. Not sold.

Peptide encoded by a mitochondrial open reading frame; studied as a metabolic signal in animals.

Mechanism not yet fully established.

Proposed mechanism: MOTS-c has been reported to influence AMPK-related metabolic signalling and exercise-like transcriptional programmes in mice. Mechanism not yet fully established as a human drug. Circulating MOTS-c measurements in humans are biomarker research, not dosing instructions.

Human pharmacology as a drug is not established to registration standard.

• Metabolic stress models

  D · Primarily animal / preclinical evidence

  Preclinical studies suggest metabolic effects in diet-induced obesity models. Human therapeutic trials of MOTS-c as a drug were not identified as an approved programme.^[1]

• Longevity / ageing biology

  E · Mechanistic / theoretical evidence only

  Mechanistic/theoretical ageing-biology interest exceeds the human interventional evidence base.^[1]

Investigational findings are not proven clinical benefits unless an authority has labelled that indication.

Overall human evidence grade: D · Primarily animal / preclinical evidence

Limited high-quality clinical data.

Animal, cell and in-vitro findings are listed separately from human effects.

• Animal experimental: Mice, diet-induced metabolic stress

  Preclinical studies suggest improved metabolic parameters in specific models.

  Limitations: Do not convert mouse doses to human self-administration.

  ^[1]

This section does not provide personalised medical dosing. Values are those reported in papers or protocols. Animal mg/kg doses are not converted to human doses.

Doses reported in human studies

Insufficient reliable evidence identified.

Preclinical / animal study dosing

1. Lee et al. 2015 MOTS-c mouse experiments

   Dose: Paper-specific mg/kg intraperitoneal mg/kg (animal)

   Route: Intraperitoneal

   Frequency: Study-specific

   Duration: Study-specific

   Model: Mice

   Purpose: Experimental metabolic pharmacology

   ^[1]

Reliable human PK for therapeutic MOTS-c injections were not identified.

Insufficient reliable evidence identified.

Unknowns. Unknowns dominate for unregulated injectables.

Contraindications. Not for human use.

Australia — TGA

Not approved.

United States — FDA

Not approved as a MOTS-c drug.

European Union — EMA

Not approved.

1. [1] The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance

   Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance Cell Metab. 2015. doi:10.1016/j.cmet.2015.02.009 PMID 25738459

   PMID 25738459DOI