SS-31

SS-31 (also known as Elamipretide, MTP-131, or Bendavia) is a synthetic aromatic-cationic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) developed by Hazel Szeto and Peter Schiller, giving it the "SS" designation. Unlike most antioxidants, SS-31 does not simply neutralize ROS systemically — it concentrates selectively at the inner mitochondrial membrane, where it binds to cardiolipin to stabilize the architecture of the electron transport chain. This targeted mechanism has generated substantial research interest across cardiac, renal, and aging biology.

Cardiolipin is a unique phospholipid found almost exclusively in the inner mitochondrial membrane. It plays a structural role in organizing the electron transport chain supercomplexes (respirasomes) that drive ATP production. When mitochondria are damaged or aged, cardiolipin becomes oxidized (peroxidized), causing cristae disorganization and impaired ETC function. SS-31 binds cardiolipin with high affinity, protecting it from peroxidation and stabilizing ETC supercomplex assembly, which researchers hypothesize underlies its observed bioenergetic effects.

Yes. Elamipretide (the clinical name for SS-31) has progressed through Phase II clinical trials. The PROGRESS-HF Phase II trial studied it in patients with heart failure with reduced ejection fraction (HFrEF). The SPYRAL trial investigated renal applications. Phase III trials have also been conducted in Barth syndrome (a rare mitochondrial cardiomyopathy). Despite clinical data, Elamipretide has not yet received FDA marketing approval for any indication.

SS-31's uptake into mitochondria is independent of the mitochondrial membrane potential, unlike many other mitochondria-targeted compounds (e.g., MitoQ). This is significant because damaged or depolarized mitochondria — the ones most in need of intervention — can still accumulate SS-31. The peptide's alternating aromatic and cationic residues facilitate spontaneous partitioning into the negatively charged inner mitochondrial membrane.

SS-31 has been studied in: ischemia-reperfusion injury models (cardiac, renal, cerebral); diet-induced and genetic models of heart failure; aged skeletal muscle function studies; models of mitochondrial disease (Barth syndrome); neurodegenerative disease models; and various oxidative stress paradigms. Human clinical data exist for cardiac and renal applications.

Store lyophilized SS-31 at -20°C, protected from light. Once reconstituted in bacteriostatic water or sterile saline, store at 2–8°C and use within 30 days. SS-31 is water-soluble and does not require DMSO for dissolution, which simplifies its handling in aqueous research systems. Always refer to published study protocols for specific concentration and vehicle guidance.