SS-31 (elamipretide)
SS-31, known as elamipretide, is a synthetic mitochondria-targeted tetrapeptide that binds the inner-membrane lipid cardiolipin. It received FDA accelerated approval in September 2025 as Forzinity for Barth syndrome.
Overview
SS-31 is one of the Szeto-Schiller peptides, a series of small aromatic-cationic peptides developed by Hazel Szeto and Peter Schiller. These peptides were found to concentrate in mitochondria despite their positive charge, and SS-31 became the lead compound for development. Under the name elamipretide it was developed by Stealth BioTherapeutics and studied in several conditions involving mitochondrial dysfunction. The aromatic-cationic design was intended to allow cell penetration while avoiding rapid degradation.
On September 19, 2025, the FDA granted accelerated approval to elamipretide as Forzinity for Barth syndrome, a rare inherited disorder of cardiolipin metabolism, in patients weighing at least 30 kg. Accelerated approval is based on an effect thought reasonably likely to predict clinical benefit and typically requires confirmatory evidence. Elamipretide has also been studied in primary mitochondrial myopathy, heart failure and age-related eye disease, with mixed results across trials.
Compare: MOTS-c vs SS-31.
Structure
SS-31 is a tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2′,6′-dimethyltyrosine, a non-standard aromatic amino acid, and the first residue is the D-enantiomer of arginine. The C-terminus is amidated. This alternating aromatic-cationic arrangement gives the peptide a net positive charge and is central to its interaction with mitochondrial membranes. The D-amino acid and non-standard residue increase resistance to proteolysis. Pharmaceutical and research material is supplied as a salt; the counter-ion should be specified.
Mechanism
SS-31 accumulates at the inner mitochondrial membrane, where it binds cardiolipin, a phospholipid that is essential for the structure of cristae and for the organization of electron transport chain complexes. Binding is proposed to stabilize cardiolipin-protein interactions, preserve cristae structure, improve the efficiency of electron transport and reduce the generation of reactive oxygen species. Earlier descriptions emphasized a direct antioxidant effect, but more recent work frames the main action as membrane stabilization. Uptake is described as independent of mitochondrial membrane potential.
Research
Barth syndrome
Barth syndrome is caused by mutations in the tafazzin gene, which disrupt cardiolipin remodeling and lead to cardiomyopathy, muscle weakness and neutropenia. Because SS-31 targets cardiolipin, Barth syndrome was a natural indication. Clinical study data in this population supported the FDA's accelerated approval of elamipretide as Forzinity in September 2025, for patients weighing at least 30 kg. Barth syndrome is very rare, so trial populations were small, which is one reason the approval took the accelerated pathway.
Primary mitochondrial myopathy
Elamipretide was studied in adults with primary mitochondrial myopathy, a group of genetic disorders affecting mitochondrial function in muscle. A phase 3 trial in this population did not meet its primary endpoints, illustrating that effects in one mitochondrial disorder do not necessarily extend to others. Further work has examined genetically defined subgroups. Interpretation of these trials is complicated by the genetic diversity of the population studied.
Heart, kidney and eye studies
Preclinical studies in rodent and large-animal models examined SS-31 in heart failure, ischemia-reperfusion injury and kidney injury, and clinical trials were conducted in some of these settings, with results that generally did not lead to approval. Elamipretide has also been studied in age-related macular degeneration. These programs show the breadth of interest in mitochondrial targeting, but outside Barth syndrome the clinical evidence remains investigational.
Aging research
In aged mice, SS-31 has been reported to improve measures of mitochondrial function and performance in skeletal and cardiac muscle. These are animal findings used to explore the role of mitochondrial decline in aging. They do not establish any effect on aging in people. Some of these studies examined treatment in old animals over weeks rather than across the lifespan, so they address reversibility of age-related changes rather than lifespan itself. Human data in aging are lacking.
Regulatory status
Elamipretide received FDA accelerated approval on September 19, 2025 as Forzinity (Stealth BioTherapeutics) for Barth syndrome in patients weighing at least 30 kg. Accelerated approval generally carries a requirement for confirmatory evidence. Uses outside the approved indication are investigational. Approval status in other countries should be checked locally. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis for SS-31 should confirm identity by mass spectrometry against the expected mass shown on this page and report HPLC purity. Compound-specific points include confirming the D-configuration of arginine, which standard MS cannot distinguish from the L-form; chiral analysis or a validated method with a D/L reference is needed to exclude the diastereomer. The presence of the non-standard Dmt residue and the C-terminal amide should be consistent with the observed mass. The salt form and net peptide content should be reported, as the peptide carries several positive charges.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized SS-31 sealed at -20 °C, protected from light and moisture. The D-amino acid and non-standard residues give good resistance to proteases, but the material is still subject to hydrolysis and moisture uptake. Allow vials to reach room temperature before opening, aliquot prepared solutions and avoid repeated freeze-thaw cycles. Cationic peptides can adsorb to surfaces at low concentrations.
Download the SS-31 (elamipretide) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention SS-31 (elamipretide) in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is SS-31 FDA approved?
Yes, for one indication. Elamipretide, the drug name for SS-31, received FDA accelerated approval on September 19, 2025 as Forzinity for Barth syndrome in patients weighing at least 30 kg. Accelerated approval generally requires further confirmatory evidence. Any other use remains investigational.
What is cardiolipin and why does SS-31 target it?
Cardiolipin is a phospholipid found almost exclusively in the inner mitochondrial membrane. It helps shape the folded cristae and holds electron transport chain complexes in their working arrangement. SS-31 binds cardiolipin and is proposed to stabilize these structures, which is why it was developed for Barth syndrome, a disorder in which cardiolipin remodeling is defective.
What does Dmt mean in the SS-31 sequence?
Dmt stands for 2′,6′-dimethyltyrosine, a tyrosine derivative with two methyl groups on the aromatic ring. It is not one of the 20 standard amino acids. In SS-31 it contributes to the alternating aromatic-cationic pattern that allows the peptide to reach and bind mitochondrial membranes, and it helps make the peptide resistant to enzymatic breakdown.
Related compounds
- MOTS-c
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, described in 2015 as a regulator of metabolic homeostasis. Research is mainly in cell and rodent models, with limited human data.
- NAD+
NAD+ (nicotinamide adenine dinucleotide) is not a peptide; it is a dinucleotide coenzyme essential for redox metabolism and a substrate for sirtuins, PARPs and CD38. It is studied in aging and metabolic research.
- Glutathione
Glutathione is a tripeptide (γ-Glu-Cys-Gly) found in nearly all cells, where it acts as a major antioxidant and redox buffer. Its glutamate is linked through the side-chain gamma carboxyl, an unusual, non-standard peptide bond.
- FOXO4-DRI
FOXO4-DRI is a synthetic D-retro-inverso peptide designed to disrupt the interaction between the transcription factor FOXO4 and p53 in senescent cells. It was described in a 2017 Cell paper as a senolytic in mice; human data are absent.
References
- PubMed: all indexed literature on SS-31 (elamipretide)
- ClinicalTrials.gov: registered studies mentioning SS-31 (elamipretide)
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