MOTS-C

Peptide Data Sheet for Pharmacists and Compounding Professionals

BASIC INFORMATION

Name: MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA type-c)
Class: Mitochondrial-derived peptide (MDP)
Structure: 16-amino acid peptide
Molecular Weight: 1618.8 g/mol
Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Origin: Encoded by the mitochondrial genome in the 12S rRNA region

Available Forms:

  • Research peptide
  • Not available as an FDA-approved medication
  • Compounded formulations (subject to regulatory restrictions)

REGULATORY STATUS

FDA Status

  • Not FDA-approved for any medical condition
  • Classified as a research compound
  • FDA has clarified it is among peptides unlawful to use in making compounded medications
  • Not a legitimate dietary ingredient and cannot legally be used in dietary supplements

Sports/Anti-Doping Status

  • Prohibited at all times under Section 4.4 Metabolic Modulators, 4.4.1. Activators of the AMP-activated protein kinase (AMPK) on the World Anti-Doping Agency Prohibited List
  • Athletes cannot get a Therapeutic Use Exemption (TUE) for MOTS-c because there is no approved therapeutic use

MECHANISM OF ACTION

MOTS-c is a mitochondrial-derived peptide that:

  • Activates the 5′-monophosphate-activated protein kinase (AMPK) pathway
  • Regulates metabolic homeostasis
  • Promotes glucose utilization in skeletal muscle
  • Enhances cellular glucose uptake
  • Increases insulin sensitivity
  • Regulates skeletal muscle metabolism and gene expression
  • Inhibits oxidative stress
  • Can activate NF-κB to inhibit inflammation
  • Transfers to the nucleus during metabolic stress to direct nuclear gene expression

The activation of AMPK leads to:

  • Increased glucose uptake via GLUT4 translocation
  • Enhanced fatty acid oxidation
  • Mitochondrial biogenesis
  • Reduced oxidative stress
Mechanism of Action

PHARMACOKINETICS

| Parameter | Value | Notes | |———–|——-|——-| | Expression | Co-expressed with mitochondria in different tissues | Present in multiple tissue types | | Circulation | Present in plasma | Levels decrease with age | | Response to Exercise | Increases ~11.9-fold in skeletal muscle following exercise | Circulating levels increase 1.6-fold during exercise | | Duration | Levels increase 1.5-fold after exercise | Return to baseline after ~4 hours |

Note: Pharmacokinetic data is primarily derived from limited human studies and animal research.

POTENTIAL APPLICATIONS (INVESTIGATIONAL)

Note: All applications are investigational and not FDA-approved. This information is provided for educational purposes only.

Metabolic

  • Insulin resistance
  • Type 2 diabetes
  • Obesity
  • Metabolic syndrome

Age-Related

  • Age-related metabolic decline
  • Sarcopenia
  • Mitochondrial dysfunction

Other Investigational Areas

  • Exercise performance enhancement
  • Cardiovascular protection
  • Neuroprotection
  • Inflammation reduction

ADMINISTRATION (INVESTIGATIONAL)

Routes

  • Subcutaneous injection (most common in research)
  • Intravenous injection (less common, research only)

Investigational Dosing

Note: No established safe or effective dosing regimen exists. The following information is based on research protocols and is not a recommendation for clinical use.

| Setting | Investigational Dose Range | Frequency | |———|—————————-|———–| | Research protocols | 5-10 mg | Daily |

SAFETY PROFILE

Reported Adverse Effects

Note: Safety data is extremely limited and primarily from anecdotal reports and animal studies.

  • Increased heart rate or heart palpitations
  • Injection site irritation
  • Insomnia
  • Fever
  • Headache
  • Nausea

Potential Risks and Concerns

  • Unknown long-term effects
  • Potential metabolic disturbances
  • Potential for growth promotion in pre-existing cancers (theoretical)
  • Lack of quality control in commercially available products
  • Potential for contamination in non-pharmaceutical grade products
  • Unknown drug interactions

Contraindications (Theoretical)

  • Active malignancy
  • Pregnancy and lactation
  • Children and adolescents
  • Uncontrolled cardiovascular disease
  • Uncontrolled diabetes

SPECIAL POPULATIONS

Pregnancy and Lactation

  • No human data available
  • Avoid use due to unknown risks

Pediatric

  • No human data available
  • Not recommended for use in pediatric populations

Geriatric

  • No specific data available
  • Potentially higher risk of adverse effects

PHARMACIST GUIDANCE

Compounding Considerations

  • FDA has clarified that MOTS-c is among peptides unlawful to use in making compounded medications
  • Pharmacists should be aware of regulatory restrictions
  • If compounding is legally permitted in specific circumstances:
    • Requires aseptic technique and sterile compounding environment
    • Stability affected by temperature and mechanical agitation
    • Adhere to USP <797> standards for sterile compounding

Storage and Handling (Research Settings)

  • Store lyophilized peptide at -20°C
  • Reconstituted solutions typically stored at 2-8°C
  • Use within 14 days of reconstitution
  • Avoid repeated freeze-thaw cycles
  • Protect from light

Patient Counseling Points

  • Not FDA-approved for any indication
  • Limited safety and efficacy data in humans
  • Unknown long-term effects
  • Potential for serious adverse effects
  • Importance of discussing all supplements and medications with healthcare providers
  • FDA has warned against its use in compounded medications
  • Athletes should be warned that it is prohibited by WADA
  • Many websites advertise MOTS-c “for research purposes only” but these products may be unsafe and illegal

ETHICAL AND PROFESSIONAL CONSIDERATIONS

For Pharmacists

  • Be aware of FDA position on MOTS-c in compounding
  • Understand legal and ethical implications of dispensing non-FDA approved peptides
  • Maintain professional standards when discussing investigational compounds
  • Provide evidence-based information when consulted about MOTS-c
  • Consider liability issues related to non-FDA approved compounds

For Researchers

  • Ensure proper informed consent in research settings
  • Follow institutional and regulatory guidelines for research peptides
  • Document and report adverse events
  • Maintain scientific integrity in research protocols

REFERENCES

  1. Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023 Jan 25;14:1120533.
  2. USADA. What is the MOTS-c peptide? January 16, 2024. https://www.usada.org/spirit-of-sport/what-is-mots-c-peptide/
  3. Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54.
  4. FDA. Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
  5. Lu H, et al. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med (Berl). 2019;97(4):473-485.