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MOTS-c

Grade D: Preclinical or anecdotal only

TL;DR: No published clinical trial of exogenously administered MOTS-c in humans exists. Human studies to date have measured naturally circulating MOTS-c levels as an observational biomarker in the context of aging, metabolic disease, and exercise; these studies describe the peptide's endogenous biology but do not test whether giving MOTS-c to a person produces any effect. The distinction is critical: a biomarker that correlates with health states in observational data is not evidence that administering the same molecule as a drug is beneficial or safe. From the standpoint of exogenous therapeutic use, MOTS-c is a preclinical compound. Grade D reflects the absence of any published interventional human evidence. A Phase 1 trial of CB4211 (a MOTS-c-based analog, safety-only, unpublished as an efficacy paper) exists but does not constitute evidence for native MOTS-c.

Key Takeaways

  • Grade D: Preclinical or anecdotal only
  • Not FDA approved: Not FDA-approved; no established compounding pathway; subject to ongoing regulatory review.
  • Compounding: The nomination to add MOTS-c to the FDA 503A or 503B bulk-substances list was withdrawn; it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding.
MOTS-c chemical structure
Structure via PubChem CID 146675088

Mechanism

MOTS-c is a mitochondria-encoded peptide proposed to regulate metabolic homeostasis by activating AMPK and influencing nuclear gene expression in response to metabolic stress.

Evidence

No published clinical trial of exogenously administered MOTS-c in humans exists. Human studies to date have measured naturally circulating MOTS-c levels as an observational biomarker in the context of aging, metabolic disease, and exercise; these studies describe the peptide's endogenous biology but do not test whether giving MOTS-c to a person produces any effect. The distinction is critical: a biomarker that correlates with health states in observational data is not evidence that administering the same molecule as a drug is beneficial or safe. From the standpoint of exogenous therapeutic use, MOTS-c is a preclinical compound. Grade D reflects the absence of any published interventional human evidence. A Phase 1 trial of CB4211 (a MOTS-c-based analog, safety-only, unpublished as an efficacy paper) exists but does not constitute evidence for native MOTS-c.

Safety and risks

Human safety data for exogenously administered MOTS-c is absent from the published literature. MOTS-c's endogenous presence in human tissue does not establish that pharmacological exogenous dosing is safe; dose, timing, route, and systemic effects at supraphysiological concentrations have not been characterized in human trials. Immunogenicity, off-target effects, and long-term consequences of exogenous administration are entirely unknown. The compound is not FDA-approved and has no established compounding pathway. Wellness-market claims for MOTS-c substantially exceed what the current evidence supports and should be disregarded without independent verification.

Interactions

No human pharmacokinetic or interaction data available. Theoretical caution with agents affecting AMPK signaling or mitochondrial function.

Federal compounding status

Nomination withdrawn (was Category 2) as of 2026-06-02.

This substance was nominated for the FDA 503A or 503B bulk-substances list and previously sat in the Category 2 (significant safety risk) group; the nomination was later withdrawn, so it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding. FDA source

Federal status only, from public FDA records. State pharmacy-board rules vary and are not covered here. This is regulatory reporting, not legal advice. All compounds.

Compounding legality

The nomination to add MOTS-c to the FDA 503A or 503B bulk-substances list was withdrawn; it is not on an active FDA bulks list and is not eligible for routine pharmacy compounding.

Sources

  1. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. (2023) review
  2. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. (2015) other
  3. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. (2023) review
  4. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. (2024) other
  5. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. (2022) other
  6. The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism. (2024) other
  7. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. (2018) other
  8. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. (2022) review
  9. The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression. (2024) other
  10. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. (2016) review
  11. MOTS-c reduces myostatin and muscle atrophy signaling. (2021) other
  12. Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane. (2024) other
  13. Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes. (2025) other
  14. Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart. (2025) other
  15. The protective effect of the mitochondrial-derived peptide MOTS-c on LPS-induced septic cardiomyopathy. (2023) other
  16. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. (2023) review
  17. The mitochondrial-derived peptide MOTS-c suppresses ferroptosis and alleviates acute lung injury induced by myocardial ischemia reperfusion via PPARĪ³ signaling pathway. (2023) other
  18. Novel function of MOTS-c in mitochondrial remodelling contributes to its antiviral role during HBV infection. (2024) other
  19. Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation. (2019) other
  20. [Effects of exercise intervention on mitochondrial-derived peptide MOTS-c in the germ cells of obese men]. (2021) review
  21. MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus. (2019) review
  22. Mitochondrial derived peptide MOTS-c prevents the development of heart failure under pressure overload conditions in mice. (2022) other
  23. Mitochondrial-Derived Peptide MOTS-c Ameliorates Spared Nerve Injury-Induced Neuropathic Pain in Mice by Inhibiting Microglia Activation and Neuronal Oxidative Damage in the Spinal Cord via the AMPK Pathway. (2023) other
  24. Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway. (2020) other
  25. MOTS-c Functionally Prevents Metabolic Disorders. (2023) review

MOTS-c is Not FDA approved. PeptideGrids presents evidence and regulatory status for informational purposes only. We do not sell, supply, source, or help anyone obtain this compound, and we provide no dosing or administration guidance. This is not medical advice; consult a licensed clinician. Full disclaimer.

Last reviewed June 2, 2026 by PeptideGrids editorial team (independently audited).