What SS-31 is
SS-31 is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt stands for 2',6'-dimethyltyrosine. Hazel Szeto and Peter Schiller developed the compound while studying opioid receptor peptides; the name comes from their initials. The alternating aromatic and cationic residues that gave the peptide its opioid activity turned out, by observation rather than design, to also concentrate it in mitochondria.
The molecule carries several names across the literature: SS-31, MTP-131, Bendavia (an earlier development name used by Stealth BioTherapeutics), and elamipretide, its international nonproprietary name. In September 2025 the FDA granted accelerated approval to an elamipretide hydrochloride formulation under the brand name Forzinity, covered in detail below. Research use of the unapproved compound predates that approval by more than twenty years and continues in parallel, across indications well outside Forzinity's approved label.
Mechanism: cardiolipin binding without relying on membrane potential
Zhao and colleagues, working with Szeto and Schiller, described the core mechanism in Journal of Biological Chemistry in 2004 (Zhao et al., J Biol Chem 2004;279:34682-34690). The peptide inhibited mitochondrial swelling, blocked oxidative cell death, and reduced reperfusion injury in isolated mitochondria and cell culture. The paper traced this back to a single binding event: SS-31 attaches to cardiolipin, a phospholipid found almost exclusively in the inner mitochondrial membrane.
A later structural study of the peptide's interaction with lipid bilayers (PMC7247319) showed that SS-31 changes the surface electrostatics of the membrane it binds, an interaction mechanically distinct from how older mitochondria-targeted antioxidants work. Compounds built on a triphenylphosphonium cation, such as MitoQ, accumulate in mitochondria by riding the transmembrane electrical potential the organelle generates. SS-31 does not depend on that potential. Its affinity for cardiolipin lets it concentrate in mitochondria that are already damaged or partially depolarized, a state in which TPP+-based compounds lose most of their uptake.
Reported accumulation runs from 1,000-fold to 5,000-fold relative to the surrounding cytosol. By binding cardiolipin directly rather than acting as a diffuse free-radical scavenger, SS-31 is thought to stabilize inner-membrane curvature and the cristae structures that depend on normal cardiolipin content.
Clinical trial evidence
Elamipretide has been tested in randomized trials across several conditions, with mixed results that depend heavily on which endpoint and which trial phase is being read.
The PROGRESS-HF trial randomized 71 patients with heart failure and reduced ejection fraction (40% or below) to placebo or one of two elamipretide doses, 4 mg or 40 mg, given daily for 28 days (Butler J et al., J Card Fail 2020;26:429-437). Neither dose produced a significant change in left ventricular end-systolic volume, the trial's primary endpoint, compared with placebo. Both doses were well tolerated.
The TAZPOWER trial in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism, produced a more complicated result. The randomized, double-blind, placebo-controlled crossover phase did not meet its co-primary endpoints, change in six-minute walk distance and total fatigue score on the Barth Syndrome Symptom Assessment, after 12 weeks (Reid Thompson W et al., Genet Med 2021;23:471-478). Ten of the original participants continued into an open-label extension without a concurrent placebo arm.
By week 168 of that extension, the eight remaining patients showed a cumulative 96.1-meter improvement in six-minute walk distance from their extension baseline, and knee extensor muscle strength improved more than 45%, correlating with the walk-distance gains (Genet Med 2024, PMID 38602181). Injection-site reactions were the most common adverse event across both phases.
The gap between the randomized-phase result and the open-label extension is the central complication in reading the Barth syndrome data. An open-label extension has no concurrent placebo arm, so improvement over that period cannot rule out regression to the mean or the effect of sustained physical therapy alongside treatment. The FDA weighed this evidence differently than a standard efficacy trial would typically require, which is the subject of the next section.
FDA approval for Barth syndrome
On September 19, 2025, the FDA granted accelerated approval to elamipretide hydrochloride, marketed as Forzinity, for Barth syndrome in patients weighing at least 30 kg. It is the first approved treatment for Barth syndrome and the first FDA-approved therapy for any primary mitochondrial disease. The approval carried Orphan Drug, Fast Track, Priority Review, and Rare Pediatric Disease designations in the United States, along with an Orphan Disease Designation from the European Medicines Agency.
Barth syndrome is caused by mutations in the TAZ gene, which encodes tafazzin, an enzyme that remodels cardiolipin in the inner mitochondrial membrane. Without functional tafazzin, cardiolipin composition is abnormal, which is why a cardiolipin-binding peptide was tested in this population in the first place. The disorder is X-linked, affects primarily males, causes cardiac and skeletal muscle complications, and is estimated to affect roughly 150 people in the United States.
Forzinity's approval does not extend to any of the other conditions elamipretide has been studied in, including heart failure, primary mitochondrial myopathy, or ischemia-reperfusion injury. It also does not apply to SS-31 sold as a research compound outside a prescription context. The molecule under investigation since 2004 and the approved, prescription-only Forzinity formulation are chemically identical, but Forzinity is dispensed through a specialty pharmacy under medical supervision for one specific, ultra-rare indication.
SS-31 research beyond Barth syndrome
Outside cardiac and Barth syndrome work, SS-31 has been studied in rodent models of chronic kidney disease, where it reduced fibrosis markers and preserved mitochondrial ultrastructure in kidney tubular cells. Ophthalmic research groups have tested it in rat glaucoma models for retinal ganglion cell protection. Separate rodent studies have examined SS-31 in models of Alzheimer's disease-associated mitochondrial dysfunction. None of these lines has produced a completed human trial as of mid-2026, and each remains preclinical.
MOTS-c is a different but adjacent mitochondrial research peptide, discovered independently by the Lee and Cohen labs at the University of Southern California rather than by Stealth BioTherapeutics. Where SS-31 is a fully synthetic peptide engineered around a cardiolipin-binding motif, MOTS-c is encoded natively within mitochondrial DNA and acts primarily on skeletal muscle glucose metabolism. Researchers working across the mitochondrial peptide category increasingly study the two together given their shared organelle target and distinct downstream biology.
Handling considerations for research use
SS-31 supplied as lyophilized powder follows the same handling logic as other short synthetic peptides. Reconstitution with bacteriostatic water, gentle mixing rather than shaking, and refrigeration of the reconstituted solution all reduce degradation risk; the reconstitution guide on this site covers the general protocol. Verifying concentration against the peptide's molecular weight before use is standard practice, and the dosing calculator here handles the concentration and volume math for a given vial and diluent volume.
Tropical storage conditions add a variable that temperate-climate protocols do not usually account for. Ambient humidity above 70%, common across Bali and Java for much of the year, accelerates degradation of an opened lyophilized vial if it is not returned to refrigeration promptly. Researchers working in Indonesia typically keep reconstituted vials refrigerated between uses and avoid leaving opened vials at room temperature during long lab sessions, a stricter version of the storage discipline used in cooler climates.