MOTS-c
updated
MOTS-c is a 16-amino-acid peptide encoded in the DNA of mitochondria, the cell's power plants, and the body makes more during exercise; it is sold online with no approved product. It is promoted for blood sugar control, endurance and reversing metabolic aging. In mice it improved glucose tolerance and insulin sensitivity, and in old mice, injections restored treadmill performance, but no credible trial has given native MOTS-c to a person; the one completed human trial tested CB4211, a different molecule. Graded B for substantial cell and animal research plus human biomarker studies.
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 |
source: MOTS-c discovery · mouse metabolism, Lee C et al. Cell Metabolism, 2015.
source: NCT03998514 · analogue, not native MOTS-c, ClinicalTrials.gov NCT03998514.
Has 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. No study in the records checked gave MOTS-c to people and measured energy or fatigue: on October 24, 2026, a PubMed search for MOTS-c with fatigue, energy or vitality limited to clinical-trial records returned 0 results, and the one ClinicalTrials.gov entry that lists MOTS-c as an intervention, the Hudson record, lists insulin-sensitivity, glucose and safety outcomes. In people, exercise raises the body's own MOTS-c in muscle and blood.
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.
source: NCT03998514 · analogue, not native MOTS-c
source: SEC filing · topline results and formulation problem, CohBar, Inc. Form 10-K for 2022, filed with the US Securities and Exchange Commission.
source: Exercise study · human measures and mouse dosing, Reynolds JC et al. Nature Communications, 2021.
source: NCT03998514 · analogue, not native MOTS-c
source: ClinicalTrials.gov · native MOTS-c records and Hudson anomaly, ClinicalTrials.gov search for MOTS-c OR CB4211, run on 8 September 2026.
source: Search · no energy trial found, PubMed search run on October 24, 2026: (MOTS-c[tiab] OR MOTSc[tiab]) AND (fatigue[tiab] OR energy[tiab] OR vitality[tiab]) AND (clinical trial[pt] OR randomized controlled trial[pt]), 0 records. ClinicalTrials.gov search for MOTS-c the same day, 9 records; only NCT07505745 lists MOTS-c as an intervention, with insulin-sensitivity, glucose, HbA1c, safety and immunogenicity outcomes.
What 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.
source: MOTS-c discovery · mouse metabolism
source: Mechanism · stress-responsive nuclear signaling, Kim KH et al. Cell Metabolism, 2018.
What is known about MOTS-c side effects, and what 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.
source: SEC filing · topline results and formulation problem
source: FDA safety page · no human exposure data, US Food and Drug Administration.
Did FDA approve MOTS-c in 2026?
FDA staff recommended against 503A bulks-list inclusion in the July 2026 review, and the advisory committee then voted 7 to 5 to recommend MOTS-c, as news reports of the meeting describe it; FDA has posted no vote record, and the cited FDA records list no approved MOTS-c drug or dosing label. WADA's 2026 Prohibited List, in effect since 1 January 2026, names MOTS-c under S4.4.1, activators of AMP-activated protein kinase, which are prohibited at all times. The 2027 list, which takes effect on 1 January 2027, keeps the same entry.
Committee review is not marketing approval. CB4211’s IND-era development also does not approve native MOTS-c or a seller product.
source: FDA 2026 briefing · MOTS-c evidence review, US Food and Drug Administration, July 2026.
source: FDA safety page · no human exposure data
source: STAT · July 2026 committee votes, Lawrence L, Todd S. STAT, 24 July 2026.
source: WADA 2026 · MOTS-c under S4.4.1, World Anti-Doping Agency, effective 1 January 2026.
source: WADA 2027 · same MOTS-c entry, World Anti-Doping Agency, effective 1 January 2027.
What doses have human studies used?
These are doses that cited human studies or FDA labels used, in the people they studied; none is a recommendation or a protocol. No published human study on file reports a dose for this compound. The animal figures on file are not human doses.
source: ClinicalTrials.gov · native MOTS-c records and Hudson anomaly
Studies 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 search for MOTS-c OR CB4211, run on 8 September 2026.
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.
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 sourceSTAT · July 2026 committee votes
News report
Lawrence L, Todd S. STAT, 24 July 2026.
The report says the committee voted 7 to 5 on 23 July 2026 to add MOTS-c to the 503A bulks list for obesity and osteoporosis, over the objections of FDA staff. It is a news account, not an FDA record: FDA's meeting page carries no vote record.
- Study design
- News report of a public meeting
A committee recommendation is non-binding and is not an approval. The vote tallies come from news coverage because FDA has posted no minutes.
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
WADA 2026 · MOTS-c under S4.4.1
Sports rule
World Anti-Doping Agency, effective 1 January 2026.
S4.4.1 lists activators of the AMP-activated protein kinase (AMPK), naming mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), under hormone and metabolic modulators prohibited at all times.
- Study design
- Binding sport rule for covered athletes
WADA 2027 · same MOTS-c entry
Sports rule
World Anti-Doping Agency, effective 1 January 2027.
The 2027 list keeps MOTS-c under S4.4.1, activators of AMP-activated protein kinase, prohibited at all times.
- Study design
- Binding sport rule for covered athletes
Search · no energy trial found
PubMed search record
PubMed search run on October 24, 2026: (MOTS-c[tiab] OR MOTSc[tiab]) AND (fatigue[tiab] OR energy[tiab] OR vitality[tiab]) AND (clinical trial[pt] OR randomized controlled trial[pt]), 0 records. ClinicalTrials.gov search for MOTS-c the same day, 9 records; only NCT07505745 lists MOTS-c as an intervention, with insulin-sensitivity, glucose, HbA1c, safety and immunogenicity outcomes.
No clinical-trial record measured energy or fatigue after MOTS-c, and the registry entry that gives MOTS-c measures metabolic and safety outcomes.
Read the original sourceWhy 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.
read MOTS-c in the reptides guide, chapter 08: 10 pages, free to read.
how tiers are graded: methodology · every cited source · about reptides.
Research reference, not medical advice. Entries distinguish product labels, study doses and reported protocols. Check the linked source for the product, route and population.