SS-31 did not start life as a mitochondrial compound. It began as peptide number 31 in a research series aimed at opioid receptors, and the property that made it interesting was almost an accident. That accident is now the reason the molecule carries several names, a clinical history spanning two decades, and a place in the story of mitochondria-targeting research.
Where SS-31 came from: the Szeto-Schiller series
In the early 2000s, Hazel Szeto at Weill Cornell Medical College and Peter Schiller at the Institut de recherches cliniques de Montréal were working on a family of small peptides. The “SS” in SS-31 comes from their surnames, and the number marks its position in the run of analogues they synthesised. The original interest was opioid pharmacology, not energy metabolism.
As the team modified the structure, they suppressed the peptides’ affinity for opioid receptors by a large margin. What remained was a short, water-soluble molecule with an unusual habit: it concentrated inside cells at the mitochondria. That behaviour, rather than any opioid activity, became the focus. The compounds were described in the literature as cell-permeable, mitochondria-targeted peptides, and by around 2004 Szeto and Schiller were publishing on their antioxidant and mitochondrial properties.
What is elamipretide, and why cardiolipin matters
SS-31 is an amphipathic tetrapeptide, meaning a four-amino-acid chain with both water-attracting and fat-attracting regions. Its sequence alternates aromatic and basic residues, and that arrangement lets it cross membranes and settle where few small molecules can reach: the inner mitochondrial membrane. There it associates with cardiolipin, a distinctive phospholipid found almost exclusively in that membrane and closely tied to how mitochondria maintain their structure and handle energy.
This cardiolipin interaction is the mechanistic thread running through most SS-31 research. Rather than being distributed evenly through the cell, the peptide is enriched at the one place where cardiolipin lives. Later structural work, including studies published around 2020, examined how it binds lipid bilayers and influences the electrostatics of the membrane surface, refining the earlier picture of a simple antioxidant.
As the molecule moved from academic laboratory toward drug development, it accumulated the names it is now known by. SS-31 is the original research designation. MTP-131 and Bendavia were development codes. Elamipretide is the international nonproprietary name assigned once it entered formal clinical study. They all refer to the same tetrapeptide.
From bench to clinic: Stealth BioTherapeutics
To carry the compound into human trials, Szeto helped found Stealth BioTherapeutics in 2006. Under the elamipretide and Bendavia names, the peptide entered a broad clinical programme across conditions where mitochondrial function was thought to play a role.
Cardiac research came early. The EMBRACE-STEMI study, a Phase 2a trial, tested intravenous elamipretide for reducing reperfusion injury in patients having a first anterior-wall heart attack. It did not meet its primary endpoint. Heart failure work followed, including the PROGRESS-HF Phase 2 trial examining left-ventricular function. Kidney and renal models, optic-nerve conditions such as Leber’s hereditary optic neuropathy, and primary mitochondrial myopathy were all studied.
The myopathy programme illustrates how uneven the results were. The MMPOWER studies reported early signals in physical capacity and fatigue measures, but the pivotal Phase 3 MMPOWER-3 trial did not meet its primary endpoints in the overall study population. This mix of encouraging secondary findings and missed primary endpoints has been a recurring pattern across the elamipretide literature.
Where the history stands today
After roughly two decades of investigation, the compound reached a milestone in 2025. On 19 September 2025, the U.S. Food and Drug Administration granted accelerated approval to elamipretide hydrochloride, marketed as Forzinity, for Barth syndrome, an ultra-rare genetic mitochondrial disorder. It was described as the first FDA-approved therapy directed at a mitochondrial disease, and the approval was narrow, covering a specific patient group rather than the wide range of conditions the peptide was once tested against.
That narrowness is the honest summary of SS-31’s history. It is a compound with a clear origin, a well-characterised affinity for cardiolipin, a long trail of clinical trials, and results that have been genuinely mixed. Its story is still being written in the research literature, and much about how it behaves in different tissues remains an open scientific question rather than a settled one.
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Research use only. This article is provided for scientific and historical reference. SS-31 is supplied by Vero Labs strictly as a research compound, not for human or animal use. Every batch is independently third-party lab-tested with a published Certificate of Analysis (COA).