Description
SS-31 (also called elamipretide or bendavia) is a synthetic tetrapeptide that binds selectively to cardiolipin in the inner mitochondrial membrane. The sequence (D-Arg-Dmt-Lys-Phe-NH2) contains modified amino acids that give the compound an unusual pharmacokinetics and tissue-specific accumulation in mitochondria. SS-31 was developed in the Hazel Szeto lab at Cornell University and is well-established in the mitochondrial community.
The research mechanism lies in the stabilization of the inner mitochondrial membrane. Cardiolipin is a unique phospholipid that occurs almost exclusively in the inner mitochondrial membrane and is essential for the correct function of the respiratory chain and ATP synthase. SS-31 binds cardiolipin and stabilizes the membrane architecture in preclinical models, leading to preserved respiratory capacity and reduced oxidative stress.
In animal models, SS-31 has been associated with effects on cardiac ischemia-reperfusion damage, age-related mitochondrial dysfunction, neurodegenerative models and nephrological research setups. The compound database is extensive, with clinical studies in phase II and III for various indications.
A particularity of SS-31: accumulation in mitochondria is approximately 1000-fold higher than in cytoplasmic concentration, making the compound a highly selective mitochondrial research tool.
SS-31 is available in 10mg, 50mg and 100mg vials as 10-vial packs.
This information is for research and educational purposes only. No medical recommendations.
Risks & Safety
SS-31 is considered well tolerated per study reports and is better documented through phase II and III clinical studies than many other peptides.
Observed in research and user reports:
- Injection site: mild redness, pressure or transient irritation at the injection site is among the most common observations. In clinical studies, local reactions were the most frequently noted observation.
- Circulation: isolated reports of brief warmth, mild dizziness or headache shortly after application.
- Selective accumulation: the strong accumulation in mitochondria is mechanistically intended, but it also means that the long-term effects of sustained mitochondrial exposure in humans are not yet conclusively characterized.
- Limited long-term data: despite clinical studies, robust data on long-term non-clinical use is lacking. The profile rests on study data and animal models.
This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.
Studies
- Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury - Journal of Biological Chemistry 2004: First description of the Szeto-Schiller peptides: cell-permeable, concentrated about 1000-fold in the inner mitochondrial membrane, with less ROS production, swelling and cytochrome c release in isolated mitochondria and improved contractile force in an ex vivo heart model.
- The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin - Journal of the American Society of Nephrology 2013: SS-31 binds cardiolipin with high affinity, inhibited the peroxidase activity of cytochrome c and protected cristae membranes in a rat model of renal ischemia, so that ATP recovered faster on reperfusion.
- Functional role of cardiolipin in mitochondrial bioenergetics - Biochimica et Biophysica Acta - Bioenergetics 2014: Review of the lipid targeted by SS-31: cardiolipin sits almost exclusively in the inner mitochondrial membrane, organizes the respiratory chain complexes into supercomplexes and is involved in mitochondrial apoptosis.
- Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice - Aging Cell 2013: A single dose of SS-31 restored mitochondrial ATP production in the skeletal muscle of aged mice to young levels within one hour. Eight days of dosing increased endurance capacity.
- First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics - British Journal of Pharmacology 2014: Review of the discovery, mechanism of action and clinical development of SS-31 as the first cardiolipin-protective compound.
