Peptide Relay

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Relay is organizing the evidence and source boundaries.

Compound library

Defined peptide

Mitochondrial-derived signaling peptide

MOTS-c

Investigational

An experimental peptide studied for how the body uses energy. People often look into it for metabolism and exercise.

5-minute readFull profile reviewed July 25, 2026

Evidence is explained by question. Dosing references show their own check dates.

60-second overview

MOTS-c at a glance

Why people look into it, what studies found, and what is still unknown.

Why people look into it: Blood sugar, energy use, exercise-related effects, and aging-related questions.
What studies found: Studies giving MOTS-c to mice found metabolic changes. Human studies mainly measured the body's own MOTS-c rather than giving the peptide.
What is still unclear: Human treatment benefits, dose, absorption, and safety remain unknown. A natural blood level linked to health does not show that adding MOTS-c helps.

About the evidence and review date

Educational information only. Evidence reviewed through July 25, 2026. Published studies, sponsor announcements, and trials without results are labeled separately. Evidence gaps apply to the specific finding beside them.

Research questions

Why people research it

Each label shows how much evidence supports that question.

Insulin sensitivityCurrently being studied
Exercise response and performanceEarly human evidence
Metabolic healthAnimal or lab research
Healthy agingAnimal or lab research
Weight lossNot demonstrated

What studies show

What the evidence supports

The research behind the answer

Human studies show that endogenous MOTS-c changes with exercise and is associated with some metabolic and vascular phenotypes. No completed controlled human efficacy results for administered native MOTS-c were publicly available at the cutoff.

See each finding and its sources (9)

Mechanistic rationale

MOTS-c is a 16-amino-acid mitochondrial-derived peptide linked to cellular energy-stress signaling.

The peptide is encoded within the mitochondrial 12S rRNA region. Laboratory work connects it with AMPK-related signaling, altered folate-purine metabolism, and stress-responsive nuclear gene expression.

FDA's 2026 review said the relevant molecular targets remain insufficiently defined. AMPK is a proposed downstream pathway, not a validated MOTS-c receptor.

Regulatory sourceNonclinical pharmacology and mechanistic limitations

Peer reviewedPeptide identification and metabolic experiments

Peer reviewedNuclear translocation and AMPK-dependent response

No direct evidence located

No completed controlled human efficacy results for administered native MOTS-c were publicly available at the evidence cutoff.

Human papers largely measure naturally occurring MOTS-c. The first sizable native-MOTS-c metabolic trial is enrolling and has no posted results.

The evidence state can change when trial results are posted. Absence of completed evidence is not proof of benefit or proof of harm.

Regulatory sourceClinical effectiveness and human-exposure review

Trial registryEnrolling status and no posted results

Other human evidence

Exercise increased endogenous MOTS-c in a 10-person human study, but this does not show that taking MOTS-c improves performance.

Researchers measured a large post-exercise increase in skeletal-muscle MOTS-c and a smaller temporary rise in blood. The participants exercised; they did not receive the peptide.

The human sample was small, young, male, and sedentary. Performance improvements after administered MOTS-c in the same paper came from mice.

Peer reviewedHuman exercise substudy and mouse intervention experiments

Other human evidence

Human circulating-level studies are associations, not evidence that MOTS-c treatment improves metabolic or cardiovascular outcomes.

Studies have reported different endogenous MOTS-c patterns in diabetes, obesity, and coronary endothelial dysfunction. Those patterns may be causes, consequences, or compensatory responses.

Heterogeneous assays, small studies, cross-sectional designs, and clinical differences limit interpretation.

Peer reviewedPooled observational results and limitations

Peer reviewedCirculating-level association

Registered trial — no results

The Phase 2a MOTS-MET trial is testing subcutaneous investigational MOTS-c, but it has no results and does not disclose the dose publicly.

The study plans to enroll 120 adults with prediabetes and overweight or obesity and test insulin sensitivity after 12 weeks.

A research route and schedule are not public-use instructions. Registration does not establish an effective dose, safety, or a recommended protocol.

Trial registryArms, route, endpoints, enrollment, and status

No direct evidence located

CB4211 human trial results cannot be treated as direct evidence for native MOTS-c.

CB4211 is described as an optimized analog derived from MOTS-c. A related molecule may inform development, but it can differ in exposure, potency, safety, and biological effects.

Analog evidence should remain clearly labeled and should not be pooled into native-MOTS-c ratings or efficacy claims.

Trial registryInvestigational product identity and study design

Animal study

Animal studies report metabolic and physical-performance signals, but human translation remains unresolved.

Experimental MOTS-c improved glucose handling and diet-related metabolic measures in mice, and later mouse work reported performance and healthspan signals.

Mouse exposure, biology, outcomes, and lifespan do not establish human efficacy, dosing, durability, or safety.

Peer reviewedMouse physical-performance and aging experiments

Peer reviewedMouse obesity and insulin-resistance experiments

No direct evidence located

MOTS-c is not FDA approved, and the July 2026 advisory vote did not grant drug approval.

The advisory committee voted 7–5, with two abstentions, to recommend possible 503A Bulks List inclusion. The vote was non-binding, final FDA action remained pending, and compounding status is separate from drug approval.

Regulatory status can change. Possible future compounding-list inclusion would not establish clinical efficacy, safety, or an approved indication.

Regulatory sourceFDA proposal and evaluation conclusion

Primary sourceJuly 23 advisory vote and non-binding status

No direct evidence located

MOTS-c is prohibited for athletes under WADA's metabolic-modulator rules.

The 2026 Prohibited List names MOTS-c in S4.4 among AMPK activators and metabolic modulators prohibited at all times.

Athletes must check every governing body that applies to them; Peptide Relay does not provide anti-doping clearance.

Regulatory sourceS4.4 Metabolic Modulators

Risks & unknowns

What needs caution

Reported side effects

Relay has not verified a clear pattern of side effects for this compound.

Evidence boundary

Human exposure is present, but the record is not detailed enough to characterize a reliable adverse-event pattern.

Missing reports do not establish safety. Findings apply to the product, route, amounts, population, comparison, and follow-up studied.

Side-effect frequency, study withdrawals, and gaps

How often side effects occurred

The available information does not reliably show how often particular side effects occur.

Evidence boundary

Under-detected or under-reported events must not be described as rare.

Why people stopped in studies

Relay has not verified which side effects led people to stop treatment in studies.

Evidence boundary

This is an evidence gap, not proof that discontinuations did not occur.

Warning information

Relay has not verified a compound-specific warning summary for this profile.

Evidence boundary

Not FDA approved. Phase 2a MOTS-MET is enrolling without results. PCAC recommended possible 503A Bulks List inclusion on July 23, 2026; final FDA action remained pending at the evidence cutoff. WADA S4.4 prohibited. Whether administered native MOTS-c improves insulin sensitivity, body composition, physical performance, or meaningful health outcomes in people, and whether repeated exposure is safe.

Emergency instructions

This profile does not contain verified, product-specific emergency instructions.

Evidence boundary

Relay does not infer emergency guidance from study discontinuations, mechanism, or incomplete adverse-event reporting.

Dosing references

Dosing & preparation

Each table labels its source and applies only to the named route, product, or study. An online example or community report is not an approved dose.

Route: SubQ · Under the skin

Evidence gap · SubQ

No verified administered-human regimen

Human measurements of naturally occurring MOTS-c do not establish an injected dose. Studies of analogues cannot supply a native MOTS-c regimen.

What would fill this gap: A verified human administration protocol for native MOTS-c, not an analogue or a calculation example.

Dosing review checked Oct 20, 2026. Additional sources are available below.

Preparation & concentration · SubQ

No route-specific preparation instructions were verified. A different route or product does not supply them.

Concentration = total mass ÷ final volume. The calculator performs user-entered math; it does not choose a dose or diluent.

Open concentration calculator

Starting dose, maintenance, and trial targets explained

Starting dose: the amount used at the beginning of the named label schedule or trial.

Maintenance: the ongoing amount described by that product label.

Trial target: the amount assigned to a study group. Different groups may stop increasing at different targets.

Other source records, populations, and limits · all routes

Preclinical evidence only

Native MOTS-c in original preclinical research

Amount in this source: A complete human regimen was not verified in this source record. See the dosing status above.
Frequency: Model-specific preclinical schedules
Route: Intraperitoneal administration in mouse models
Duration: Varied by laboratory experiment

Population, study design, and limitations

The original administration research located for this pass used mouse models. FDA's 2026 review identified no publicly available clinical study or human exposure record for administered MOTS-c-related substances.

Population: Laboratory mouse models; no verified administered-human population

Design: Original laboratory and mouse experiments

Animal exposure does not establish a human amount, route, efficacy result, or safety profile.
No verified human reconstitution, administration, pharmacokinetic, or stability evidence was located.

MOTS-c: a mitochondrial-encoded regulator of metabolic homeostasisOriginal mouse and laboratory experiments FDA 2026 PCAC review materials for BPC-157 and MOTS-cBPC-157 clinical review and MOTS-c evidence review

Mechanisms

How it works

MOTS-c is a mitochondrial-derived microprotein encoded within the 12S rRNA region. Preclinical work links it to folate-purine metabolism, AICAR accumulation, AMPK-related signaling, skeletal-muscle glucose handling, and stress-induced nuclear gene regulation. A validated cell-surface receptor has not been established. Human evidence is dominated by small endogenous-biomarker and observational studies; controlled efficacy and repeated-exposure safety for administered native MOTS-c remain unresolved.

Why this matters

A plausible mechanism can explain why a study was attempted. It does not prove that the compound improves a human outcome.

Signals and targets

Proposed biological steps

Proposed AMPK-linked cellular energy sensing
Folate-purine pathway modulation and AICAR accumulation
Stress-induced nuclear translocation and gene regulation
Proposed skeletal-muscle glucose-metabolism effects

Research reference

How mature is the evidence?

A reference for the studies, populations, and routes behind this profile.

Research depthEarly human-development stage

Human administration research is limited to an enrolling Phase 2a trial with no posted results; the completed human record measures endogenous MOTS-c rather than giving the peptide.

Why this matters

Research depth describes how large and mature the overall record is. It does not tell you whether the results were positive.

Evidence confidenceVery low for human treatment outcomes

Metabolic and exercise findings are primarily mouse, cell, or observational biomarker evidence, and native MOTS-c has no completed human efficacy dataset.

Why this matters

Confidence describes how reliable and consistent the conclusions are. It can be high for one outcome and low for another.

Strongest evidenceAn enrolling 120-person Phase 2a trial plus human biomarker studies

Why this matters

The strongest evidence type shows what the best-supported conclusions are actually based on.

Human evidenceNo completed native-MOTS-c administration outcome study

Why this matters

Human findings are more directly relevant than animal or laboratory results, but they still apply only to the populations and outcomes studied.

Route-specific record

Which product or study does this describe?

Native MOTS-c in original preclinical researchAmounts and schedules below belong to this source record.MOTS-c: a mitochondrial-encoded regulator of metabolic homeostasis FDA 2026 PCAC review materials for BPC-157 and MOTS-c Administration reference reviewed Aug 5, 2026

Route studiedIntraperitoneal administration in mouse models

Schedules studiedModel-specific preclinical schedules; Varied by laboratory experiment

Amounts studiedWithheld for this route, formulation, identity, or model

Why this matters

These are exposures used in cited research for a specific route and population—not an instruction for an individual.

Half-lifeNot established for this exact record

Why this matters

Half-life describes how long it takes the measured amount in the body to fall by half. It is not a dosing recommendation.

Route evidenceThe original administration research located for this pass used mouse models. FDA's 2026 review identified no publicly available clinical study or human exposure record for administered MOTS-c-related substances.

Why this matters

Evidence can change by administration method. Findings from one route should not automatically be applied to another.

Evidence boundary: Animal exposure does not establish a human amount, route, efficacy result, or safety profile. No verified human reconstitution, administration, pharmacokinetic, or stability evidence was located. Amounts shown describe cited research exposure—not a dosage recommendation.

Studies

Study-by-study record

Study arms are reported for transparency. They describe what researchers did in a defined record and do not transfer across identities, routes, formulations, or populations.

Why this matters

A later trial phase can ask a more mature question, but it does not guarantee a positive result, regulatory approval, or relevance outside the studied population.

Other human evidencePeer reviewed

The correlation between mitochondrial derived peptide level and metabolic parameters: a systematic review and meta-analysis

Peer reviewed

PhaseSystematic review and meta-analysis of observational studies

Population602 participants

DurationCross-sectional or case-control measurements

Design and population

Meta-analysis of six case-control studies and one cross-sectional study examining circulating mitochondrial-derived peptides and metabolic measures

People with and without diabetes or obesity across 11 comparison groups

Outcomes measured

Circulating MOTS-c concentration
Diabetes status
Obesity status
Correlations with metabolic measures

What was reported

Pooled results associated lower circulating MOTS-c with diabetes but higher levels with obesity. The directions differed by metabolic condition.

Study administration and important limits

Study administration: No MOTS-c administration; studies measured endogenous circulating levels

Limitations: Small heterogeneous observational studies cannot determine whether MOTS-c causes, compensates for, or merely accompanies metabolic differences. They do not test MOTS-c treatment.

Other human evidencePeer reviewed

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Peer reviewed

PhaseHuman exercise physiology substudy

Population10 participants

DurationSingle exercise session with measurements through 4 hours

Design and population

Acute exercise study measuring the body's endogenous MOTS-c before, during, and after stationary cycling

Healthy, sedentary young men

Outcomes measured

Endogenous MOTS-c in skeletal muscle
Circulating endogenous MOTS-c
Time course after exercise

What was reported

Skeletal-muscle MOTS-c increased about 11.9-fold after exercise, while circulating levels rose more modestly during and shortly after exercise before returning toward baseline.

Study administration and important limits

Study administration: Stationary-bicycle exercise; participants were not administered MOTS-c

Limitations: This was a 10-person biomarker study in young men. It shows an endogenous response to exercise, not that injected MOTS-c improves exercise performance or health.

Laboratory studyPeer reviewed

Mitochondrial-encoded MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress

Peer reviewed

PhaseMechanistic laboratory study

PopulationNot disclosed

DurationAcute laboratory experiments

Design and population

Cell-based metabolic-stress experiments examining MOTS-c localization and gene-expression responses

Cultured human cells

Outcomes measured

Nuclear translocation
Nuclear gene expression
AMPK dependence
Cellular stress resistance

What was reported

MOTS-c moved into the nucleus during metabolic stress and influenced adaptive nuclear gene expression in an AMPK-dependent manner.

Study administration and important limits

Study administration: Metabolic stress with experimental MOTS-c pathway manipulation

Limitations: A cellular mechanism does not establish a validated human molecular target, clinical effect, or safe treatment strategy.

Other human evidencePeer reviewed

Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction

Peer reviewed

PhaseObservational human study

PopulationNot disclosed

DurationSingle clinical assessment

Design and population

Cross-sectional measurement of circulating endogenous MOTS-c in people undergoing invasive coronary endothelial-function testing

Adults evaluated for coronary endothelial dysfunction

Outcomes measured

Circulating endogenous MOTS-c
Coronary endothelial function
Cardiovascular risk characteristics

What was reported

Lower circulating MOTS-c was associated with coronary endothelial dysfunction.

Study administration and important limits

Study administration: No MOTS-c administration

Limitations: The study was observational and cannot show that low MOTS-c caused dysfunction or that administering MOTS-c would improve cardiovascular outcomes.

Animal studyPeer reviewed

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

Peer reviewed

PhasePreclinical discovery study

PopulationNot disclosed

DurationShort-term laboratory and animal experiments

Design and population

Cell experiments and mouse metabolic studies, including high-fat-diet models

Cultured cells and mice

Outcomes measured

Cellular glucose metabolism
AMPK-related signaling
Diet-induced obesity
Insulin sensitivity

What was reported

The study identified MOTS-c as a 16-amino-acid mitochondrial-derived peptide and reported improved metabolic measures in experimental models, including protection against diet-induced obesity and insulin resistance in mice.

Study administration and important limits

Study administration: Experimental MOTS-c exposure in cells and mice

Limitations: Cell and mouse results establish biological plausibility, not efficacy, dose, or safety in humans.

Registered trial — no resultsTrial registry

MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

Trial registry

PhasePhase 2a — enrolling

Population120 participants

Duration12-week double-blind treatment period plus 4-week post-treatment safety follow-up

Design and population

Randomized, quadruple-blind, placebo-controlled, parallel-group trial with 1:1 allocation and standardized lifestyle counseling

Adults aged 18–65 with prediabetes and BMI 27–40 kg/m²

Outcomes measured

Change in OGTT-derived Matsuda insulin-sensitivity index at week 12
Treatment-emergent adverse events through week 16
HbA1c and fasting glucose
Two-hour OGTT glucose
Lipids, body weight, and waist circumference
Anti-drug antibodies and other safety assessments

What was reported

No results are posted. This trial is designed to test whether native investigational MOTS-c improves insulin sensitivity in people rather than only in animal or cell models.

Study administration and important limits

Study administration: Subcutaneous investigational MOTS-c or matching placebo; the public registration does not disclose the MOTS-c dose

Limitations: An enrolling registration does not demonstrate benefit or safety. Enrollment, completion, results, peer review, and replication remain pending.

Community

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2015-03-03 · PMID 25738459 · DOI 10.1016/j.cmet.2015.02.009

Peer reviewed

Profile identity

MOTS-c

Aliases: Mitochondrial open reading frame peptide, Mitochondrial open reading frame of the 12S rRNA type-c, Mitochondrial-derived peptide MOTS-c, MOTS-c free base, MOTS-c acetate

Targets: No validated cell-surface receptor, AMPK pathway — proposed downstream signaling, not a receptor

Evidence maturity: Early human endogenous-biomarker evidence; native-MOTS-c controlled efficacy results unavailable; most treatment evidence remains preclinical

Regulatory status: Not FDA approved. Phase 2a MOTS-MET is enrolling without results. PCAC recommended possible 503A Bulks List inclusion on July 23, 2026; final FDA action remained pending at the evidence cutoff. WADA S4.4 prohibited.

Reviewed: July 25, 2026

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MOTS-c

MOTS-c at a glance

Why people research it

What the evidence supports

MOTS-c is a 16-amino-acid mitochondrial-derived peptide linked to cellular energy-stress signaling.

No completed controlled human efficacy results for administered native MOTS-c were publicly available at the evidence cutoff.

Exercise increased endogenous MOTS-c in a 10-person human study, but this does not show that taking MOTS-c improves performance.

Human circulating-level studies are associations, not evidence that MOTS-c treatment improves metabolic or cardiovascular outcomes.

The Phase 2a MOTS-MET trial is testing subcutaneous investigational MOTS-c, but it has no results and does not disclose the dose publicly.

CB4211 human trial results cannot be treated as direct evidence for native MOTS-c.

Animal studies report metabolic and physical-performance signals, but human translation remains unresolved.

MOTS-c is not FDA approved, and the July 2026 advisory vote did not grant drug approval.

MOTS-c is prohibited for athletes under WADA's metabolic-modulator rules.

What needs caution

Dosing & preparation

No verified administered-human regimen

Preparation & concentration · SubQ

Native MOTS-c in original preclinical research

How it works

Signals and targets

Proposed biological steps

How mature is the evidence?

Which product or study does this describe?

Study-by-study record

The correlation between mitochondrial derived peptide level and metabolic parameters: a systematic review and meta-analysis

Design and population

Outcomes measured

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Design and population

Outcomes measured

Mitochondrial-encoded MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress

Design and population

Outcomes measured

Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction

Design and population

Outcomes measured

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

Design and population

Outcomes measured

MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

Design and population

Outcomes measured

Experience reports stay separate from published evidence

Help strengthen the MOTS-c experience record

Keep the question moving

Trace every major statement

FDA evaluation of MOTS-c-related bulk drug substances for the July 2026 Pharmacy Compounding Advisory Committee

US FDA advisers weigh restrictions on seven peptides as industry presses expansion

MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

2026 World Anti-Doping Code International Standard Prohibited List

The correlation between mitochondrial derived peptide level and metabolic parameters: a systematic review and meta-analysis

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

A Study of CB4211 in Healthy Non-obese Subjects and Subjects With Non-alcoholic Fatty Liver Disease

Mitochondrial-encoded MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress

Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction

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