Metabolic & GLP-1PeptideEvidence B2 cited

MOTS-c

Mitochondrial-Derived Peptide

aka MOTS-c mitochondrial peptide · mitochondrial ORF of the 12S rRNA type-c

A mitochondria-encoded peptide research associates with AMPK activation, metabolic flexibility, and exercise capacity.

Molecular wt

2174.6g/mol

Formula

C101H152N28O22S2

CAS

1627580-64-6

Half-life

4 h

estimated

Tmax

1 h

Route

Subcutaneous injection

PubChem

146675088

Sequence

One-letter16 residues

MRWQEMGYIFYPRKLR

Three-letter

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg

Read this before quoting the sequence

16-residue mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA gene. Linear, free acid C-terminus (PubChem records it as H-MRWQEMGYIFYPRKLR-OH). No disulfide or cyclisation.

Source ↗

Mechanism of action

MOTS-c is a mitochondrial-derived peptide that influences cellular metabolism by activating the AMPK pathway, which enhances glucose uptake and fatty acid oxidation. It also modulates the expression of genes involved in metabolism and stress response, promoting mitochondrial biogenesis and function. This peptide can improve insulin sensitivity and energy expenditure, contributing to metabolic health.

What the evidence actually shows

Grade B

There are a limited number of human trials on MOTS-c, with preliminary studies indicating improvements in metabolic markers and exercise performance. However, larger and more comprehensive studies are needed to confirm these effects and understand long-term safety. | REGULATORY: FDA Category 2 reclassification to Category 1 expected (announced Feb 2026).

Regulatory status

Status

Not approved as a medicine in any jurisdiction.

Clinical stage

Preclinical. No published trial of MOTS-c administered to humans was identified in PubMed/Europe PMC searches; the human literature consists of observational studies measuring endogenous circulating MOTS-c.

research_compound

In the UK, MOTS-c is considered a research compound and is not approved for clinical use by the MHRA.

Source ↗

Pharmacokinetics

Half-life

4 h

Tmax

1 h

Absorption

subcutaneous

Elimination

renal

Washout

3 days

Low-confidence pharmacokinetics

These figures are recorded as estimated rather than measured in a published PK study. Treat them as an order of magnitude. Anything downstream of them — accumulation, steady state, washout — inherits that uncertainty.

Dosing — what backs each figure

No published human dose of MOTS-c exists. A Phase 2 trial in prediabetes (NCT07505745) is recruiting with a once-daily subcutaneous 'fixed dose' for 12 weeks, but the dose itself is not disclosed. Everything currently circulating comes from mouse studies using 5-15 mg/kg/day by intraperitoneal injection.

PreclinicalAnimal studies — not a human dose

5 or 15 mg/kg/day by intraperitoneal injection for 2 weeks (normal-diet and high-fat-diet young mice, and middle-aged/old mice); also 15 mg/kg 3x weekly from 13.5 and 23.5 months of age for late-life healthspan endpoints
mouse (CD-1, C57BL/6J, C57BL/6N) · intraperitoneal · PMID 33473109
MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity (original characterisation study)
mouse · intraperitoneal · PMID 25738459

Animal doses do not convert to human doses by body weight alone. Route matters too — a compound dosed intraperitoneally in mice tells you little about subcutaneous use.

Commonly circulatedNot established by any study

Dose: Research literature cites ~5 to 10 mg per dose in protocols
Frequency: 2-3x weekly

Why this isn't evidence
No human study has published a MOTS-c dose, and the '5 to 10 mg' figure looks like the mouse 5-15 mg/kg/day intraperitoneal number read as a flat human milligram dose - a 5 mg/kg mouse dose does not translate to 5 mg in a person by any accepted scaling method.

This figure is shown because it is what circulates and what people search for — not because it is supported. Cycle lengths in particular tend to be convention copied between compounds rather than anything derived from a compound's own pharmacokinetics.

No established human dose

No approved label or completed human trial establishes a dosing regimen for this compound. Anything presented as a standard protocol for it — anywhere — is someone's convention rather than a finding.

Handling and storage

No compound-specific stability data exists

No peer-reviewed or regulatory stability data specific to MOTS-c was located. There is no approved product and no label. Only generic lyophilised-peptide handling guidance exists. Note the sequence contains two methionine residues, which are oxidation-prone in solution, but no published study quantifying this for MOTS-c was found. General peptide handling still applies — reconstitute gently, keep it cold, keep it dark — but any specific figure you see quoted for this compound elsewhere is someone's assumption, not a measurement.

→ Reconstitution walkthrough → Reconstitution calculator

Safety

Commonly reported

·Injection site irritation
·Mild headache

Rarely reported

·Allergic reactions

Contraindications

·Pregnancy
·Breastfeeding
·"Severe liver or kidney disease"

Drug interactions

·Metformin: May enhance glucose-lowering effects through similar pathways

Limited human data

Reported combinations

Reported as synergistic

·Berberine
·Resveratrol

Reported as antagonistic

·High-dose antioxidants: May blunt exercise-induced mitochondrial adaptations

Combination claims in this dataset are largely unsourced and should be treated as folk knowledge until a citation appears beside them.

References (2)

Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance ↗
Cell MetabPMID 25738459DOI
Original description of MOTS-c. In mice, MOTS-c activated AMPK via inhibition of the folate/methionine cycle and prevented diet-induced obesity and insulin resistance. Animal and cell work only.
Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. (2021) MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis ↗
Nat CommunPMID 33473109DOI
MOTS-c administration improved physical performance in young, middle-aged and old mice and regulated nuclear gene expression and skeletal muscle metabolism; MOTS-c is induced by exercise. Mouse study with human observational exercise data.

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
storage.lyophilized, storage.reconstituted, storage.lightSensitive, reconstitution.solvent, regulatory.wada

Research use only

This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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