SS-31
A mitochondria-targeted tetrapeptide studied for cardiolipin binding, mitochondrial function, and tissue protection in cardiovascular and renal research.
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What is SS-31?
SS-31 (Szeto-Schiller peptide 31), also known by its clinical development name elamipretide, is a small synthetic tetrapeptide designed to selectively accumulate in mitochondria where it binds to cardiolipin, a unique phospholipid found almost exclusively in the inner mitochondrial membrane. The peptide was developed by Hazel Szeto and Peter Schiller at Cornell University as part of a research program examining mitochondria-targeted therapeutic peptides. Its structure includes the unusual amino acids D-arginine and 2,6-dimethyltyrosine, which contribute to both its mitochondrial targeting and its ability to penetrate cell membranes.
SS-31 is notable in research as a mechanistically distinct approach to supporting mitochondrial function. Rather than acting through nuclear receptors or signaling cascades, SS-31 directly binds cardiolipin to stabilize the inner mitochondrial membrane and the protein complexes embedded within it, particularly the electron transport chain. The compound has advanced through multiple clinical trial programs by Stealth BioTherapeutics in conditions including primary mitochondrial myopathy, Barth syndrome, dry age-related macular degeneration, and heart failure, with mixed efficacy results across these diverse research contexts.
Mechanism of action
SS-31’s mechanisms of action have been investigated across multiple pathways:
- Cardiolipin binding: The peptide selectively binds cardiolipin, the signature phospholipid of the inner mitochondrial membrane, providing the basis for its mitochondrial targeting and structural effects.
- Mitochondrial membrane stabilization: By binding cardiolipin, SS-31 stabilizes inner mitochondrial membrane structure and the protein complexes within it, supporting efficient electron transport chain function.
- ATP production support: Research has documented preservation or restoration of ATP production in models of mitochondrial dysfunction, with effects on multiple complexes of the electron transport chain.
- Reduced reactive oxygen species: The peptide reduces mitochondrial reactive oxygen species production, both directly through structural effects on the electron transport chain and through preservation of normal mitochondrial function that minimizes electron leak.
- Selective mitochondrial accumulation: SS-31 accumulates in mitochondria at concentrations several-fold higher than cytoplasmic concentrations, achieved without requiring active transport mechanisms.
These pathways are characterized in both preclinical models and human clinical research.
Research applications
SS-31 has been investigated across several research domains, with the most active areas including:
- Primary mitochondrial disease research: SS-31 has been most extensively studied in primary mitochondrial myopathy and Barth syndrome, with the MMPOWER and other clinical trial programs examining effects on exercise capacity and quality of life in these populations.
- Cardiovascular research: Studies have examined effects in heart failure (PROGRESS-HF and other trials), ischemia-reperfusion injury, and acute coronary syndromes, with mechanistic interest based on the central role of mitochondrial dysfunction in cardiovascular pathology.
- Renal research: SS-31 has been studied in models of acute kidney injury, including contrast-induced nephropathy and ischemia-reperfusion injury in kidney transplantation, with research suggesting protective effects on tubular cell function.
- Ophthalmologic research: Clinical trials have examined SS-31 in dry age-related macular degeneration, with the ReCLAIM studies producing mixed efficacy results.
- Skeletal muscle and aging research: Research has examined effects on muscle function, mitochondrial efficiency, and exercise capacity in aged populations and models of sarcopenia.
This compound is intended for laboratory research use only. It has not been approved for human therapeutic use by any regulatory agency.
Storage & reconstitution
In its lyophilized form, SS-31 tolerates ambient temperatures during shipping but should be stored long-term at -20°C, protected from light. Properly stored lyophilized peptide remains stable for 24 months or longer.
Once reconstituted with bacteriostatic water for injection, SS-31 solutions should be stored refrigerated at 2-8°C and used within 28 days. Avoid repeated freeze-thaw cycles, which can degrade peptide structure and reduce activity.
Visual inspection should be performed before each use. The reconstituted solution should be clear and colorless. Reject any solution that appears cloudy, discolored, or contains visible particulate matter.
For step-by-step reconstitution calculations, see our reconstitution calculator.
For laboratory research use only. The compound described on this page is intended exclusively for in vitro research and laboratory experimentation by qualified researchers and is not for human or veterinary use. It is not a drug, food, dietary supplement, or cosmetic, and has not been approved by the FDA, Health Canada, EMA, or any other regulatory authority for the diagnosis, treatment, cure, mitigation, or prevention of any disease or medical condition. The information provided on this page is for educational and reference purposes only and does not constitute medical advice. By accessing this content you confirm that you are a qualified researcher purchasing for legitimate laboratory purposes.