CEDAR

Scientific Reference

SS-31 (Elamipretide)

Evidence profile: Human Phase 3 evidence

SS-31, also known as Elamipretide or Bendavia, is a small aromatic-cationic tetrapeptide that selectively targets the inner mitochondrial membrane. Unlike traditional antioxidants that scavenge reactive oxygen species diffusely, SS-31 specifically binds to cardiolipin — a phospholipid critical for maintaining the structural integrity of the electron transport chain — protecting it from oxidative damage and restoring cellular energy production. This targeted mechanism makes SS-31 highly relevant in mitochondrial dysfunction, cardiovascular disease, and age-related decline. It has received regulatory approval for specific mitochondrial disorders, representing the first class of therapies directly targeting mitochondrial membrane integrity rather than downstream oxidative damage.

Mechanism of Action

SS-31 selectively binds to cardiolipin in the inner mitochondrial membrane, preventing lipid peroxidation and preserving the structural integrity of the electron transport chain. This stabilisation maintains cristae architecture, optimises cytochrome c interaction, and restores efficient oxidative phosphorylation and ATP synthesis. Unlike conventional antioxidants, SS-31 localises directly to the site of mitochondrial reactive oxygen species production, providing targeted protection.

Molecular Information

  • Type: Aromatic-cationic tetrapeptide — mitochondria-targeted
  • Length: 4 amino acids
  • Molecular weight: 639.8 g/mol
  • Molecular formula: C32H49N9O5
  • CAS: 736992-21-5

Published Research

  • Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER

    Thompson WR et al. · Genetics in medicine : official journal of the American College of Medical Genetics · 2024 · Clinical

    PMID 38602181 — View on PubMed

  • Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

    Karaa A et al. · Neurology · 2023 · Clinical

    PMID 37268435 — View on PubMed