MOTS-c

A 16-amino-acid peptide encoded within mitochondrial DNA.

Preclinical-heavyPeptide research profile

Also known as: Mitochondrial ORF of the 12S rRNA-c

(how we review)

Open the calculator

Dosing & scaling, explained

The 10-15 mg entries are recorded research presets, not human trial-established doses for native MOTS-c. This is educational source context, not a protocol or recommendation.

How sourced amounts are organized

  1. Starting pointNot clinically establishedNo validated titration window

    There is no regulator-approved starting dose for this research use. A low-looking number is not automatically safe.

  2. Recorded preset10-15 mg / dayCalculator library reference

    This is the range represented in the in-app protocol library. It describes the source record; it does not validate the regimen.

  3. Higher exposureAbove 15 mg / day is not characterizedRisk and uncertainty increase

    Higher exposure is not established as more effective. Human pharmacokinetic and long-term safety data may be absent.

Drug amount and device markings are different quantities. The calculator converts mass into volume, syringe units, or pen clicks.

Patterns described in source material

  • Daily in recorded presets

    The cadence represented by the recorded calculator presets.

  • Exercise-timed in some source records

    Published experiments may use a different route, formulation, timing, or population and should not be treated as interchangeable.

  • No universal schedule

    No single schedule has been validated across products or research contexts.

Clinical context

No completed peer-reviewed dose-ranging efficacy trial establishes a native MOTS-c regimen.

Storage, handling and interpretation

Lyophilized material

Keep cold, dry, and protected from light according to the manufacturer certificate or validated lab SOP.

After reconstitution

Use sterile technique, refrigerate as validated, and avoid repeated freeze-thaw cycles.

Traceability

Record lot, concentration, preparation date, and the identity/purity documentation used by the lab.

Reported protocols for MOTS-c

What published studies and recent community write-ups report about amounts, timing and course length. 2 clinical, 2 preclinical and 3 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.

ContextDoseFrequencyRouteCourseSource
Clinical2 rows
CB4211 analog, phase 1a/1b (a modified MOTS-c, not the native peptide)65 healthy adults (single and multiple ascending doses) and 20 obese adults with at least 10% liver fat25 mg (phase 1b)Once dailySubcutaneous4 weeks, with participants housed in the study unitNot applicableCohBar, Inc. (GlobeNewswire)2021
The sponsor's topline release reported no serious adverse events, falls in ALT (21% versus a 4% rise on placebo), AST (28% versus 11%) and glucose (6% versus none), and a trend toward lower weight, while liver fat fell similarly in both groups. The results were never published in a peer-reviewed journal, the study had been paused earlier over persistent painless injection-site bumps, and the molecule is an engineered analog rather than MOTS-c.
Phase 2a trial in prediabetes (registered, recruiting; no results)120 planned adults with prediabetes and overweight or obesityUndisclosed fixed dose (the registry states only a fixed dose once daily for 12 weeks)Once dailySubcutaneous12 weeks of treatment, 4 weeks of safety follow-upNot applicableClinicalTrials.gov2026
Registered by Hudson Biotech and recruiting from February 2026, this quadruple-blind placebo-controlled study measures insulin sensitivity from an oral glucose tolerance test plus HbA1c, lipids and waist circumference. It is the first interventional trial of native MOTS-c in people and had posted no results as of this writing.
Preclinical2 rows
Preclinical discovery paper, insulin sensitivity and diet-induced obesityYoung and 12-month-old C57BL/6 mice; outbred CD-1 mice on a 60% fat diet5 mg/kg per day for 7 days (insulin sensitivity studies); 0.5 mg/kg per day for 8 weeks (high-fat diet study)Once daily (an acute 4-day twice-daily arm was also run)Intraperitoneal injection7 days or 8 weeksNot applicableCell Metabolism (PubMed Central)2015
Seven days of 5 mg/kg improved glucose clearance and raised the glucose infusion rate during clamps by about 30%, with the effect traced to skeletal muscle, and restored insulin-stimulated glucose uptake in muscle from 12-month-old mice to young levels. Eight weeks of 0.5 mg/kg prevented weight gain, hyperinsulinemia and liver fat in mice on a high-fat diet without changing how much they ate.
Preclinical exercise-capacity and aging study (with human exercise sampling)Young CD-1 and C57BL/6J mice, mice on a high-fat diet, and 12- and 22-month-old C57BL/6N mice; plus plasma and muscle sampling from sedentary young men after cycling5 mg/kg per day (young mice) or 15 mg/kg per day (high-fat diet and old mice); 15 mg/kg three times weekly for late-life treatmentDaily for 2 weeks, then three times weekly from about 24 months of age in the lifespan armIntraperitoneal injection2 weeks of daily dosing; late-life intermittent treatment continued for lifeNot applicableNature Communications2021
Two weeks at 15 mg/kg improved treadmill time and distance in old mice, and intermittent dosing begun at roughly 24 months improved grip strength, gait and walking tests and trended toward longer life. The human part was observational: endogenous MOTS-c rose in muscle and plasma after exercise in young men, which is the origin of the exercise-mimetic label; no person received the peptide.
Community-reported3 rows
Community standard protocol5 mg2-3 times per weekSubcutaneous4-8 weeksNone specified beyond the cycle endCommunity resource2026
This 2026 guide calls 5 mg two or three times a week the pattern most often discussed and gives tiers of 5 mg twice weekly for 4 weeks, 5 mg three times weekly for 4-6 weeks and 10 mg two or three times weekly for 6-8 weeks. It states that none of the tiers has been validated in a human randomized trial and that CB4211 safety data transfer only partly to the native peptide.
Community higher tier10 mg2-3 times per weekSubcutaneous6-8 weeksNone specifiedCommunity resource2026
The same guide's upper tier doubles the per-injection dose for longer cycles and notes that MOTS-c left FDA Category 2 on 22 April 2026 without being added to the compounding bulks list, and that WADA bans it at all times. It describes the available human evidence as a few cross-sectional and small studies.

How a course is commonly described

  1. Week 1Community-reported

    Community courses open with 5 mg injected subcutaneously two or three times in the first week, often before a training session because of the exercise-induced biology in mice. Injection-site irritation and transient fatigue or palpitations are the anecdotal early complaints; nothing measurable is expected this soon.

  2. Weeks 2-6Community-reported

    The 5-10 mg, two-to-three-times-weekly rhythm continues, or is collapsed into a single 10 mg weekly dose before endurance work. Users describe gradual changes in energy, endurance and fasting glucose that take weeks to notice and are entangled with the exercise they are doing at the same time.

  3. Weeks 6-10 and breakCommunity-reported

    Most frameworks end between 6 and 10 weeks, with the higher 10 mg tier reserved for the longer cycles. Sources do not agree on an off period and give no evidence for one, since no human study has dosed the peptide for more than four weeks.

  4. Preclinical comparisonPreclinical

    The mouse studies behind the community protocols used daily intraperitoneal injections of 0.5-15 mg/kg for one to eight weeks, and the late-life regimen that improved healthspan was 15 mg/kg three times a week for the rest of the animals' lives. Scaled to a human these are tens of milligrams per dose, not the 5-10 mg sold in vials, and the route was never subcutaneous.

  5. Clinical comparisonClinical

    The only human course to date used the analog CB4211 at 25 mg subcutaneously every day for four weeks in 20 people confined to a study unit, with liver enzymes and glucose as the readouts. The first trial of MOTS-c itself plans 12 weeks of daily dosing at an undisclosed amount and will not report before 2027.

  • No completed human trial of MOTS-c exists. The community schedules are extrapolated from mouse injections and from a four-week study of a different molecule, CB4211, whose results were only ever released by the company and whose developer has since dissolved.
  • The FDA's compounding entry stated that it had identified no human exposure data for MOTS-c by any route and did not know whether it would cause harm; the peptide's removal from Category 2 in April 2026 followed withdrawal of the nomination rather than new safety data. MOTS-c is prohibited at all times by WADA as an AMPK activator under S4.4.1.
  • Dose scaling is the central uncertainty: the mouse doses that worked translate to roughly 0.4 mg/kg or more in people, several times a typical 5 mg vial, while the only human exposure (25 mg daily of an analog) used a stabilized molecule. The rows above describe what sources report, not validated regimens.
Sources for this section (8)
  1. The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin ResistanceCell Metabolism (PubMed Central)2015Preclinical
  2. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasisNature Communications2021Preclinical
  3. CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and ObesityCohBar, Inc. (GlobeNewswire)2021Clinical
  4. MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity (NCT07505745)ClinicalTrials.gov2026Clinical
  5. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety RisksU.S. Food and Drug Administration2026Clinical
  6. The 2026 Prohibited List, World Anti-Doping CodeWorld Anti-Doping Agency2026Clinical

Plus 2 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.

Overview

MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame hidden inside the 12S ribosomal RNA gene of mitochondrial DNA, first described in 2015 by Changhan Lee and Pinchas Cohen's group at the University of Southern California. In mice it activates AMPK, improves insulin sensitivity, prevents diet-induced obesity and, when given to old animals, improves running capacity and healthspan, and in young men its plasma level rises after a bout of cycling; it is sold online as an exercise mimetic on the strength of that work. No human trial of MOTS-c itself has been completed: a related analog, CB4211, finished a phase 1a/1b study in 2021 before its developer dissolved, and a phase 2a trial of MOTS-c in prediabetes began recruiting in 2026. WADA prohibits it at all times as an AMPK activator (S4.4.1), and the FDA listed it among compounding substances that may present significant safety risks from 2023 until the nomination was withdrawn in April 2026, noting that it had found no human exposure data at all.

What researchers are exploring

These themes describe recurring questions in published research. They are not claims of effectiveness or recommendations for use.

  • 1

    Metabolic homeostasis

    Cell and mouse studies examine glucose handling, insulin sensitivity, and AMPK-linked signaling.

  • 2

    Exercise response

    Human observational work studies circulating MOTS-c and exercise-related physiology.

  • 3

    Stress adaptation

    Laboratory studies describe nuclear translocation during metabolic stress.

  • 4

    Healthy aging

    Age-associated expression and physical function remain exploratory research areas.

What the current evidence can support

Study models remain visible so laboratory and animal findings are not mistaken for established human outcomes.

  • Animal

    Discovery and metabolic mouse models

    The foundational Cell Metabolism study reported effects in diet- and age-related mouse models.

  • In vitro

    Folate-purine-AMPK pathway

    Mechanistic work links MOTS-c to cellular metabolic stress responses.

  • Review

    Human intervention gap

    Reviews emphasize that therapeutic human evidence remains limited and clinical development is ongoing.

Amounts recorded for MOTS-c

These amount records are independent from vial strength, reconstitution volume and measuring device. A recorded source is not the same as study backing, and these values are not recommendations.

  • 1
    DoseSign in for schedule, duration and source context.
    500 mcg
  • 2
    DoseSign in for schedule, duration and source context.
    5 mg
  • 3
    Usable recorded referenceSign in for schedule, duration and source context.
    10 mg

Chemistry identifiers

Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.

Sequence

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

Also listed as

Mitochondrial open reading frame of the 12S rRNA type-c, MOTS-c (human), Mitochondria-derived peptide MOTS-c, H-MRWQEMGYIFYPRKLR-OH, UNII A5CV6JFB78, MOTS-c trifluoroacetate salt (PubChem synonym for the same record)

InChIKey

WYTHCOXVWRKRAH-LOKRTKBUSA-N

Origin / design

Encoded by a short open reading frame in mitochondrial 12S rRNA

IUPAC name

(4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid

Limitations and unknowns

Important limitations

  • Associations between endogenous MOTS-c levels and human traits do not establish effects of administered peptide.
  • Completed, peer-reviewed human efficacy trials of native MOTS-c are not yet available.
  • A calculator preset is a recorded research convention, not a recommendation or evidence of clinical benefit.
  • Identity, purity, sterility, and stability can vary substantially outside regulated manufacturing.
  • Route, formulation, and population can make results from one study inapplicable to another use.

Sources

2 curated references, each with its journal, year and study model, plus 2 community resources reported but not linked.

  1. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistanceCell Metabolism2015Animal
  2. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and agingJournal of Translational Medicine2023Review

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