SS-31, also known as elamipretide or MTP-131, is a mitochondria-targeted tetrapeptide that homes to the inner mitochondrial membrane and stabilizes cardiolipin. Research spans cardiac aging, hypertensive cardiomyopathy, and skeletal muscle decline.
SS-31 is a synthetic tetrapeptide belonging to the Szeto-Schiller (SS) family of mitochondria-targeted compounds, named for its developers Hazel Szeto and Peter Schiller. Its sequence is D-Arg-2',6'-Dmt-Lys-Phe-NH2, where 2',6'-Dmt denotes 2',6'-dimethyltyrosine. The alternating aromatic and cationic residues allow it to penetrate cell membranes and concentrate selectively in the inner mitochondrial membrane, driven by the large electrochemical gradient across that membrane. Once there, it binds cardiolipin, a phospholipid unique to the inner mitochondrial membrane that is essential for organizing the electron transport chain complexes. [1]
Cardiolipin stabilization is the proposed central mechanism. When cardiolipin is oxidized (a consequence of mitochondrial oxidative stress), electron transport chain efficiency falls and reactive oxygen species production increases in a self-amplifying cycle. SS-31 interrupts this cycle by scavenging electrons before they can react with oxygen and by preserving cardiolipin's structural role. The compound is also known as elamipretide in clinical development (where it was studied under the name MTP-131 or Bendavia) and has been evaluated in Phase II trials for heart failure with preserved ejection fraction. It is not FDA-approved for any indication.
SS-31's evidence base spans a wide range of preclinical models and has progressed further into human trials than most research peptides, though it remains without an approved indication. The EMPOWER-HF Phase II trial and related studies examined elamipretide in heart failure with preserved ejection fraction (HFpEF), a condition where mitochondrial dysfunction is increasingly recognized as a driver. Results from those trials informed the mechanistic picture but did not yield an FDA approval. [1] [2]
The strongest mechanistic data come from rodent cardiac models and isolated mitochondria preparations from both rodents and human samples. The skeletal muscle ADP sensitivity findings are notable because they used human tissue, lending translational weight to the preclinical cardiac and neurological data. [5] Researchers reviewing this compound should distinguish between the rich in vitro and animal literature and the smaller, still-developing human clinical dataset. The research-grade compound sold by peptide vendors is not equivalent to the pharmaceutical-grade formulations used in clinical trials.
| Parameter | Detail |
|---|---|
| Common vial sizes | 5 mg, 10 mg |
| Supplied as | Lyophilized (freeze-dried) powder |
| Reconstitution | Sterile saline (0.9% NaCl) or sterile water |
| Storage (lyophilized) | Refrigerated (2–8°C); stable at -20°C long-term; avoid repeated freeze-thaw |
| Administration studied | Subcutaneous injection and intravenous infusion in clinical trials; subcutaneous in most animal studies [3] |
| Mitochondrial targeting | Concentrates in inner mitochondrial membrane driven by membrane potential; no external targeting sequence required [1] |