SS-31 (elamipretide) is a synthetic tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, that concentrates in the inner mitochondrial membrane and binds cardiolipin. By binding cardiolipin it was reported to keep cytochrome c working as an electron carrier rather than a peroxidase. Animal studies observed effects in models of lung fibrosis, inflammation-related memory impairment and anaesthesia injury.
For research purposes only. Not for human consumption. This article is educational and references published laboratory research; it is not medical advice and does not describe an approved use of any compound.
Evidence grade
- Grade ASS-31 (elamipretide)
Several randomised human trials (MMPOWER-3, TAZPOWER, PROGRESS-HF and others). Results were mixed: MMPOWER-3 missed its primary endpoints, while Barth syndrome studies reported improvements.
SS-31 is a synthetic tetrapeptide from the Szeto-Schiller family, also known as elamipretide, MTP-131 and Bendavia. It is one of the few research peptides that has been through large randomised clinical trials, with mixed results. This guide sets out where SS-31 comes from, how its binding to cardiolipin is described, what was observed in animal models and human trials, and where the published evidence stops.
Where does SS-31 come from?
SS-31 belongs to the Szeto-Schiller peptides, a series of small synthetic peptides designed by Hazel Szeto and Peter Schiller. The series alternates aromatic residues with basic amino acids, a pattern that lets the peptides cross cell membranes and gather in mitochondria without relying on the membrane potential. SS-31 itself is the tetrapeptide D-Arg-Dmt-Lys-Phe-NH2. Dmt is 2',6'-dimethyltyrosine, an altered tyrosine, and the first residue is the D form of arginine, which makes the peptide more resistant to breakdown by enzymes. The calculated molecular weight is about 640 g/mol.
In clinical development the compound took the name elamipretide, and it has also been called MTP-131 and Bendavia. A 2025 review described it as a tetrapeptide with uptake into many cell types and highly selective targeting of mitochondria.
How is it described at the molecular level?
The central target is cardiolipin, a phospholipid found almost only in the inner mitochondrial membrane. Cardiolipin shapes the cristae, the folds of that membrane, and helps the respiratory complexes assemble into supercomplexes for efficient oxidative phosphorylation. A 2014 review by Szeto described SS-31 binding cardiolipin through electrostatic and hydrophobic interactions.
The same review explained why that binding matters. Cytochrome c normally carries electrons between respiratory complexes. When it interacts with cardiolipin in a certain way it can turn into a peroxidase, which damages cardiolipin itself. SS-31 was reported to block that conversion while keeping the electron carrying function. Later reviews summarised the downstream effects observed in models as stabilised cristae, less oxidative stress and more ATP production.
What has been observed in published research?
- Lung fibrosis (mouse): in a bleomycin model, SS-31 given every other day reduced fibrosis, extracellular matrix deposition and inflammatory cytokines, and lowered IL-1beta and IL-18 by inhibiting the NLRP3 inflammasome in macrophages.
- Inflammation-related memory impairment (mouse): after lipopolysaccharide exposure, mice given elamipretide showed better learning and memory performance, less hippocampal oxidative stress and less loss of dendritic spines.
- Anaesthesia exposure (developing rat): rat pups exposed to isoflurane for six hours on day 7 of life showed less accumulation of reactive oxygen species and mitochondrial damage in the hippocampus, and better later cognitive test results, when given elamipretide beforehand.
- Primary mitochondrial myopathy (human trial): MMPOWER-3 randomised 218 adults to elamipretide or placebo for 24 weeks. It did not meet its primary endpoints, the six minute walk test and total fatigue score, and treatment was reported as well tolerated.
- Barth syndrome (human trial and case reports): in the 168 week open-label extension of TAZPOWER, the six minute walk distance improved by a cumulative 96.1 metres, with reactions at the administration site the most common adverse events. A 2026 case report described a five year old whose left ventricular ejection fraction rose from 20 to 50 percent over six months.
- Regulatory status: a 2026 review of trials in primary mitochondrial diseases listed elamipretide among four therapies with regulatory authorisation, with US accelerated approval for Barth syndrome. Another 2026 review stated that the approval covered muscle strength and that an effect on heart disease remained unconfirmed.
What the evidence does not establish
SS-31 is unusual among research peptides because its human data include a large, negative phase 3 trial. MMPOWER-3 showed that a credible mechanism and positive early studies do not guarantee a measurable effect in a broader patient group. The Barth syndrome findings come from a very rare disease, from small numbers (ten patients entered the extension) and partly from open-label designs, which are more open to bias than blinded comparisons.
Animal studies cover a wide range of organs, but each model is narrow and many come from single laboratories. None of these results describe the effect of research-grade material in any setting outside the laboratory, and the approved medicine is a regulated product, not the research material described on this site.
Which formats does Vitality Peps supply?
Vitality Peps supplies SS-31 (elamipretide) as a 10 mg lyophilised vial for laboratory research, documented by a batch certificate of analysis. Bacteriostatic water is listed separately for reconstitution. MOTS-c, another peptide studied in mitochondrial research, is available as a 40 mg vial.
How is it handled in the laboratory?
Lyophilised SS-31 is stored cold and protected from light. Before use the vial is brought to room temperature and the powder is reconstituted with bacteriostatic water, added slowly down the side of the vial and swirled rather than shaken. The working concentration is calculated from the actual vial mass on the certificate. Reconstituted solution is refrigerated, labelled and dated.
Research use only
SS-31 supplied by Vitality Peps is for in vitro laboratory research only. Not a medicine, not a supplement, not for human or veterinary consumption. Nothing above is instructions for use.
Frequently asked questions
Are SS-31 and elamipretide the same compound?
Yes. SS-31 is the research name from the Szeto-Schiller peptide series, and elamipretide is the international non-proprietary name used in clinical trials. The same molecule has also appeared as MTP-131 and Bendavia. It is a tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine, and it carries an amidated C terminus.
What is cardiolipin and why does SS-31 bind it?
Cardiolipin is a phospholipid found almost only in the inner mitochondrial membrane. It helps shape the cristae and holds the respiratory complexes together. Reviews describe SS-31 binding cardiolipin through electrostatic and hydrophobic interactions. That binding was reported to stop cardiolipin from turning cytochrome c into a peroxidase while preserving its role in electron transport.
What did the MMPOWER-3 trial find?
MMPOWER-3 was a phase 3, randomised, double-blind, placebo-controlled trial in 218 adults with genetically confirmed primary mitochondrial myopathy. After 24 weeks it did not meet its primary endpoints: the difference in six minute walk distance was minus 3.2 metres and fatigue scores did not differ. The authors reported that elamipretide was well tolerated, with mostly mild to moderate adverse events.
What has been reported in Barth syndrome?
Barth syndrome is a rare X-linked disorder of cardiolipin remodelling. In the open-label extension of the TAZPOWER trial, eight of ten patients reached 168 weeks, and the six minute walk distance improved by a cumulative 96.1 metres from extension baseline. A 2026 case report described improved heart function in a five year old child, and a 2026 review described accelerated approval in the United States.
How is SS-31 different from MOTS-c?
SS-31 is a synthetic tetrapeptide that physically binds a lipid in the inner mitochondrial membrane. MOTS-c is a natural 16 residue peptide encoded in mitochondrial DNA and described as a signal acting through AMPK and nuclear genes. SS-31 has been tested in randomised human trials, while MOTS-c evidence is mostly from mice. The comparison guide sets them side by side.
How is SS-31 handled in the laboratory?
The lyophilised powder is kept cold and protected from light until use. It is reconstituted with bacteriostatic water at room temperature, and the working concentration is calculated from the actual mass on the batch certificate rather than the label alone. Reconstituted solution is refrigerated, labelled and dated, as described in the storage and reconstitution guides.
For research purposes only. Not for human consumption. This article is educational and references published laboratory research; it is not medical advice and does not describe an approved use of any compound.
References
- First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics (Br J Pharmacol, 2014)
- Elamipretide: a review of its structure, mechanism of action, and therapeutic potential (Int J Mol Sci, 2025)
- Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial (Neurology, 2023)
- Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER (Genet Med, 2024)
- Elamipretide in pediatric Barth syndrome: from heart failure to school return (Orphanet J Rare Dis, 2026)
- Clinical development in primary mitochondrial diseases at a translational inflection point (Biomed Pharmacother, 2026)
- Mitochondrial quality control in inherited mitochondrial cardiomyopathy (Int J Mol Sci, 2026)
- Elamipretide(SS-31) attenuates idiopathic pulmonary fibrosis by inhibiting the Nrf2-dependent NLRP3 inflammasome in macrophages (2023)
- Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice (2019)
- Elamipretide (SS-31) ameliorates isoflurane-induced long-term impairments of mitochondrial morphogenesis and cognition in developing rats (Front Cell Neurosci, 2017)