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MOTS-c

Also known as: Mitochondrial Open Reading Frame of the 12S rRNA-c, Mitochondrial-derived peptide type-c

FDA Banned (Category B)

Molecular Formula

C101 H152 N28 O22 S2

Molecular Weight

2,174.62 Da

Half-Life

~1–2 hours (circulation); 85–90% degradation within 2–3 hours at room temperature

Sequence

MRWQEMGYIFYPRKLR (H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH)

Clinical Applications & Evidence

Mechanism of Action

Inhibits the folate-methionine cycle to drive AICAR accumulation and downstream AMPK activation. Facilitates robust GLUT4 membrane translocation. Downregulates muscle-wasting myostatin via the CK2-PTEN-mTORC2-AKT-FOXO1 pathway. Competitively binds Raptor to inhibit mTORC1, suppressing Th1 differentiation and T-cell glycolysis. Systemically suppresses pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) while upregulating anti-inflammatory mediators (IL-10). Induces retrograde nuclear signaling via ARE, ATF1, and JUND transcription factors.

Investigated Uses

  • Type 2 Diabetes Mellitus
  • Prediabetes and obesity
  • Nonalcoholic steatohepatitis (NASH)
  • Sarcopenia and muscle atrophy
  • Postmenopausal osteoporosis
  • Autoimmune disorders (Type 1 Diabetes)
  • Traumatic brain injury
  • Polycystic Ovary Syndrome (PCOS)
Early Clinical / Animal Models

Regulatory & Safety Status

FDA Status

FDA Banned (Category B)

WADA / Athletic Status

Prohibited in Competition

Known Side Effects

Persistent injection site irritation (painless bumps)Transient heart palpitationsMild initial fatigueLocalized flushingFeverInsomnia (if administered late in circadian cycle)

Contraindications

  • Professional athletes subject to WADA testing
  • Active cancer diagnosis
  • Pregnancy or breastfeeding
  • Severe unmonitored kidney or liver disease

Drug Interactions

  • AMPK-activating pharmaceuticals (Metformin, Thiazolidinediones, Aspirin) — overlapping, potentially unsafe
  • GLP-1 receptor agonists (investigated synergy for lean mass preservation during rapid weight loss)

Citations & Clinical Trials

ClinicalTrials.gov MOTS-c for Improving Insulin Sensitivity World Anti-Doping Agency WADA 2026 Prohibited List FDA Bulk Drug Substances Used in Compounding Under Section 503A GlobeNewswire / CohBar CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 PubMed Central MOTS-c reduces the inflammatory response in LPS-induced septic cardiomyopathy