MOTS-c
MOTS-c is a 16-amino-acid peptide encoded within mitochondrial 12S rRNA. Human studies mostly measure the body’s own MOTS-c. The completed drug trial tested CB4211, an engineered analogue, not the native MOTS-c sequence sold online.
mitochondrial-derived peptide
- Canonical sequence MRWQEMGYIFYPRKLR
- Direct administration evidence is mainly in rodents
- CB4211 is an analogue with a separate human record
- No FDA-approved MOTS-c drug
Is CB4211 the same peptide as MOTS-c?
Native MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA. CB4211 is an engineered analogue with its own formulation, pharmacokinetics, and clinical-development record.
| Intervention | What exists in humans | Limit |
|---|---|---|
| Native-sequence MOTS-c | Endogenous measurements and observational associations | No validated exogenous regimen or clinical outcome |
| CB4211 analogue | Completed Phase 1a/1b program with sponsor-reported topline data | Exact native MOTS-c efficacy, safety, or dose |
MOTS-c discovery · mouse metabolism
Cell and animal study
Lee C et al. Cell Metabolism, 2015.
The study identified a 16-amino-acid peptide encoded in mitochondrial 12S rRNA and reported effects on metabolic homeostasis, obesity, and insulin resistance in cell and mouse experiments. It did not administer MOTS-c to people.
- Participants / model
- Cell systems and mice, including diet-induced metabolic models
- Treatment
- Synthetic native-sequence MOTS-c in experimental systems
- Study design
- Discovery, mechanistic, and animal intervention study
NCT03998514 · analogue, not native MOTS-c
Clinical trial registry record
ClinicalTrials.gov NCT03998514.
The completed trial enrolled 88 participants across single- and multiple-ascending-dose cohorts and a small NAFLD cohort. It administered subcutaneous CB4211, an engineered MOTS-c analogue. The registry has no posted results and does not disclose the actual dose values.
- Participants / model
- Healthy non-obese adults and adults with obesity and nonalcoholic fatty liver disease
- Treatment
- CB4211 or placebo by subcutaneous injection
- Follow-up
- Single dose, seven-day repeat-dose, and four-week NAFLD portions
- Study design
- Randomized, double-blind, placebo-controlled Phase 1a/1b
- Funding
- CohBar, Inc.
Results from CB4211 cannot be assigned to native-sequence MOTS-c.
Read the original sourceHas native MOTS-c been administered in a credible human trial?
No credible completed trial has administered native MOTS-c to people. Human papers measure endogenous MOTS-c, NCT03998514 administered CB4211, and the nominal Hudson registry entry belongs to a cluster containing fictional, mock, or copied records and has no results.
Measuring a peptide before and after exercise shows association with human physiology. It does not establish absorption, pharmacokinetics, safety, or benefit after giving a synthetic product.
What did the CB4211 study report?
The sponsor reported short-term changes in ALT, AST, and glucose in a very small four-week NAFLD cohort, along with persistent injection-site reactions and a formulation judged unsuitable for further development. The registry itself posts no results.
NCT03998514 · analogue, not native MOTS-c
Clinical trial registry record
ClinicalTrials.gov NCT03998514.
The completed trial enrolled 88 participants across single- and multiple-ascending-dose cohorts and a small NAFLD cohort. It administered subcutaneous CB4211, an engineered MOTS-c analogue. The registry has no posted results and does not disclose the actual dose values.
- Participants / model
- Healthy non-obese adults and adults with obesity and nonalcoholic fatty liver disease
- Treatment
- CB4211 or placebo by subcutaneous injection
- Follow-up
- Single dose, seven-day repeat-dose, and four-week NAFLD portions
- Study design
- Randomized, double-blind, placebo-controlled Phase 1a/1b
- Funding
- CohBar, Inc.
Results from CB4211 cannot be assigned to native-sequence MOTS-c.
Read the original sourceSEC filing · topline results and formulation problem
Sponsor regulatory filing
CohBar, Inc. Form 10-K for 2022, filed with the US Securities and Exchange Commission.
CohBar reported topline biomarker changes after four weeks, disclosed that the trial had been suspended in 2018 because of injection-site reactions, and later said the Phase 1b formulation was not suitable for further development. These are sponsor-reported CB4211 results, not peer-reviewed native MOTS-c data.
- Participants / model
- CB4211 Phase 1a/1b participants
- Treatment
- CB4211 analogue
- Follow-up
- Up to four weeks in the Phase 1b portion
- Study design
- Company report of trial and program status
- Funding
- CohBar, Inc.
The cited sources include no peer-reviewed clinical report or posted registry results.
Read the original sourceExercise study · human measures and mouse dosing
Translational human-observation and animal study
Reynolds JC et al. Nature Communications, 2021.
The paper linked MOTS-c to exercise and age-related muscle biology, measured human exercise-related signals, and reported that administering MOTS-c improved physical performance in mice of different ages. The human component did not test MOTS-c as a drug.
- Participants / model
- Human observational samples plus young, middle-aged, and old mice
- Treatment
- Exercise observations in humans; MOTS-c intervention in mice
- Study design
- Translational study with separate human and animal components
A human biomarker response is not human administration.
Read the original sourceNCT03998514 · analogue, not native MOTS-c
Clinical trial registry record
ClinicalTrials.gov NCT03998514.
The completed trial enrolled 88 participants across single- and multiple-ascending-dose cohorts and a small NAFLD cohort. It administered subcutaneous CB4211, an engineered MOTS-c analogue. The registry has no posted results and does not disclose the actual dose values.
- Participants / model
- Healthy non-obese adults and adults with obesity and nonalcoholic fatty liver disease
- Treatment
- CB4211 or placebo by subcutaneous injection
- Follow-up
- Single dose, seven-day repeat-dose, and four-week NAFLD portions
- Study design
- Randomized, double-blind, placebo-controlled Phase 1a/1b
- Funding
- CohBar, Inc.
Results from CB4211 cannot be assigned to native-sequence MOTS-c.
Read the original sourceClinicalTrials.gov · native MOTS-c records and Hudson anomaly
Clinical trial registry
ClinicalTrials.gov records for MOTS-c and related analogues.
The cited records include CB4211, observational studies that measure endogenous MOTS-c, and NCT07505745 under Hudson Biotech. The Hudson record belongs to the same suspect sponsor batch containing self-described fictional or mock records and copied unrelated development identifiers. It is treated as a registry anomaly, not confirmed native-MOTS-c administration.
The cited ClinicalTrials.gov and primary records include no credible completed trial administering native MOTS-c.
Read the original sourceWhat does native MOTS-c do in experiments?
In cell and mouse studies, native MOTS-c altered metabolic-stress signaling and improved selected glucose, insulin-resistance, obesity, and physical-performance measures. Human therapeutic translation remains untested.
MOTS-c moved to the nucleus during metabolic stress and influenced gene expression in experimental systems. No human treatment study has established a clinical effect from that pathway.
Is it an exercise replacement?
No human trial tested that claim. The exercise paper combines human observational measurements with mouse intervention. Mouse treadmill performance does not establish a drug effect on human endurance.
Exercise study · human measures and mouse dosing
Translational human-observation and animal study
Reynolds JC et al. Nature Communications, 2021.
The paper linked MOTS-c to exercise and age-related muscle biology, measured human exercise-related signals, and reported that administering MOTS-c improved physical performance in mice of different ages. The human component did not test MOTS-c as a drug.
- Participants / model
- Human observational samples plus young, middle-aged, and old mice
- Treatment
- Exercise observations in humans; MOTS-c intervention in mice
- Study design
- Translational study with separate human and animal components
A human biomarker response is not human administration.
Read the original sourceMOTS-c discovery · mouse metabolism
Cell and animal study
Lee C et al. Cell Metabolism, 2015.
The study identified a 16-amino-acid peptide encoded in mitochondrial 12S rRNA and reported effects on metabolic homeostasis, obesity, and insulin resistance in cell and mouse experiments. It did not administer MOTS-c to people.
- Participants / model
- Cell systems and mice, including diet-induced metabolic models
- Treatment
- Synthetic native-sequence MOTS-c in experimental systems
- Study design
- Discovery, mechanistic, and animal intervention study
Mechanism · stress-responsive nuclear signaling
Cell and animal mechanism study
Kim KH et al. Cell Metabolism, 2018.
Under metabolic stress, MOTS-c moved to the nucleus and altered nuclear gene expression in experimental systems. The study did not administer MOTS-c to people or measure a clinical outcome.
- Participants / model
- Cell systems and mice
- Treatment
- Experimental MOTS-c exposure and stress conditions
- Study design
- Mechanistic molecular study
Exercise study · human measures and mouse dosing
Translational human-observation and animal study
Reynolds JC et al. Nature Communications, 2021.
The paper linked MOTS-c to exercise and age-related muscle biology, measured human exercise-related signals, and reported that administering MOTS-c improved physical performance in mice of different ages. The human component did not test MOTS-c as a drug.
- Participants / model
- Human observational samples plus young, middle-aged, and old mice
- Treatment
- Exercise observations in humans; MOTS-c intervention in mice
- Study design
- Translational study with separate human and animal components
A human biomarker response is not human administration.
Read the original sourceWhat are the main safety unknowns?
Native-MOTS-c human pharmacokinetics, dose-response, immunogenicity, repeated-use safety, pregnancy effects, and organ-specific risks remain unknown. CB4211’s injection-site problem is a warning about its analogue and formulation, not a measured event rate for native MOTS-c.
- Analogue transfer: CB4211 cannot supply a native-MOTS-c safety profile.
- Metabolic signaling: changes in glucose handling could matter alongside diabetes drugs, fasting, illness, or exercise, but interactions have not been characterized.
- Product quality: synthetic research products add sequence, concentration, sterility, endotoxin, and degradation uncertainty.
SEC filing · topline results and formulation problem
Sponsor regulatory filing
CohBar, Inc. Form 10-K for 2022, filed with the US Securities and Exchange Commission.
CohBar reported topline biomarker changes after four weeks, disclosed that the trial had been suspended in 2018 because of injection-site reactions, and later said the Phase 1b formulation was not suitable for further development. These are sponsor-reported CB4211 results, not peer-reviewed native MOTS-c data.
- Participants / model
- CB4211 Phase 1a/1b participants
- Treatment
- CB4211 analogue
- Follow-up
- Up to four weeks in the Phase 1b portion
- Study design
- Company report of trial and program status
- Funding
- CohBar, Inc.
The cited sources include no peer-reviewed clinical report or posted registry results.
Read the original sourceFDA safety page · no human exposure data
FDA safety communication
US Food and Drug Administration.
FDA reports no human exposure data for drug products containing MOTS-c and cites immunogenicity, peptide-impurity, and API-characterization concerns.
- Study design
- Agency safety summary
The FDA assessment concerns MOTS-c itself rather than CB4211.
Read the original sourceDid FDA approve MOTS-c in 2026?
FDA staff recommended against 503A bulks-list inclusion in the July 2026 review, and the cited FDA records list no approved MOTS-c drug or dosing label.
Committee review is not marketing approval. CB4211’s IND-era development also does not approve native MOTS-c or a seller product.
FDA 2026 briefing · MOTS-c evidence review
FDA staff briefing document
US Food and Drug Administration, July 2026.
FDA staff separated MOTS-c from related analogues, reviewed the mainly nonclinical evidence and human safety gap, and recommended against 503A bulks-list inclusion. The advisory process did not approve MOTS-c.
- Study design
- Regulatory evidence review
FDA safety page · no human exposure data
FDA safety communication
US Food and Drug Administration.
FDA reports no human exposure data for drug products containing MOTS-c and cites immunogenicity, peptide-impurity, and API-characterization concerns.
- Study design
- Agency safety summary
The FDA assessment concerns MOTS-c itself rather than CB4211.
Read the original sourceStudies and sources
MOTS-c discovery · mouse metabolism
Cell and animal study
Lee C et al. Cell Metabolism, 2015.
The study identified a 16-amino-acid peptide encoded in mitochondrial 12S rRNA and reported effects on metabolic homeostasis, obesity, and insulin resistance in cell and mouse experiments. It did not administer MOTS-c to people.
- Participants / model
- Cell systems and mice, including diet-induced metabolic models
- Treatment
- Synthetic native-sequence MOTS-c in experimental systems
- Study design
- Discovery, mechanistic, and animal intervention study
Mechanism · stress-responsive nuclear signaling
Cell and animal mechanism study
Kim KH et al. Cell Metabolism, 2018.
Under metabolic stress, MOTS-c moved to the nucleus and altered nuclear gene expression in experimental systems. The study did not administer MOTS-c to people or measure a clinical outcome.
- Participants / model
- Cell systems and mice
- Treatment
- Experimental MOTS-c exposure and stress conditions
- Study design
- Mechanistic molecular study
Exercise study · human measures and mouse dosing
Translational human-observation and animal study
Reynolds JC et al. Nature Communications, 2021.
The paper linked MOTS-c to exercise and age-related muscle biology, measured human exercise-related signals, and reported that administering MOTS-c improved physical performance in mice of different ages. The human component did not test MOTS-c as a drug.
- Participants / model
- Human observational samples plus young, middle-aged, and old mice
- Treatment
- Exercise observations in humans; MOTS-c intervention in mice
- Study design
- Translational study with separate human and animal components
A human biomarker response is not human administration.
Read the original sourceNCT03998514 · analogue, not native MOTS-c
Clinical trial registry record
ClinicalTrials.gov NCT03998514.
The completed trial enrolled 88 participants across single- and multiple-ascending-dose cohorts and a small NAFLD cohort. It administered subcutaneous CB4211, an engineered MOTS-c analogue. The registry has no posted results and does not disclose the actual dose values.
- Participants / model
- Healthy non-obese adults and adults with obesity and nonalcoholic fatty liver disease
- Treatment
- CB4211 or placebo by subcutaneous injection
- Follow-up
- Single dose, seven-day repeat-dose, and four-week NAFLD portions
- Study design
- Randomized, double-blind, placebo-controlled Phase 1a/1b
- Funding
- CohBar, Inc.
Results from CB4211 cannot be assigned to native-sequence MOTS-c.
Read the original sourceSEC filing · topline results and formulation problem
Sponsor regulatory filing
CohBar, Inc. Form 10-K for 2022, filed with the US Securities and Exchange Commission.
CohBar reported topline biomarker changes after four weeks, disclosed that the trial had been suspended in 2018 because of injection-site reactions, and later said the Phase 1b formulation was not suitable for further development. These are sponsor-reported CB4211 results, not peer-reviewed native MOTS-c data.
- Participants / model
- CB4211 Phase 1a/1b participants
- Treatment
- CB4211 analogue
- Follow-up
- Up to four weeks in the Phase 1b portion
- Study design
- Company report of trial and program status
- Funding
- CohBar, Inc.
The cited sources include no peer-reviewed clinical report or posted registry results.
Read the original sourceClinicalTrials.gov · native MOTS-c records and Hudson anomaly
Clinical trial registry
ClinicalTrials.gov records for MOTS-c and related analogues.
The cited records include CB4211, observational studies that measure endogenous MOTS-c, and NCT07505745 under Hudson Biotech. The Hudson record belongs to the same suspect sponsor batch containing self-described fictional or mock records and copied unrelated development identifiers. It is treated as a registry anomaly, not confirmed native-MOTS-c administration.
The cited ClinicalTrials.gov and primary records include no credible completed trial administering native MOTS-c.
Read the original sourceFDA safety page · no human exposure data
FDA safety communication
US Food and Drug Administration.
FDA reports no human exposure data for drug products containing MOTS-c and cites immunogenicity, peptide-impurity, and API-characterization concerns.
- Study design
- Agency safety summary
The FDA assessment concerns MOTS-c itself rather than CB4211.
Read the original sourceFDA 2026 briefing · MOTS-c evidence review
FDA staff briefing document
US Food and Drug Administration, July 2026.
FDA staff separated MOTS-c from related analogues, reviewed the mainly nonclinical evidence and human safety gap, and recommended against 503A bulks-list inclusion. The advisory process did not approve MOTS-c.
- Study design
- Regulatory evidence review
Why is MOTS-c in B tier?
The B grade reflects substantial cell and animal research plus human biomarker studies. Native MOTS-c has no credible administered-human trial, and CB4211 is a different molecule.