SS-31 (elamipretide): a cardiolipin-binding peptide

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Prepared by: Research Desk. Sources are linked for verification.

Published 19 October 2026

At a glance

Type: synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2)
Other names: elamipretide, MTP-131, Bendavia
Research stage: extensive preclinical work; several clinical trials
Regulatory status: FDA accelerated approval in September 2025 for one rare disease (brand name Forzinity); research-grade SS-31 is not that approved product

What SS-31 is

SS-31 is a small synthetic peptide of four amino acids: D-arginine, 2',6'-dimethyltyrosine (Dmt), lysine and phenylalanine, with an amidated C-terminus. It belongs to the Szeto-Schiller (SS) peptides, named after Hazel Szeto and Peter Schiller, who developed the series. The alternating aromatic and positively charged residues let the peptide cross cell membranes and concentrate in the inner mitochondrial membrane.

Research history

The SS peptides were first developed in the context of opioid receptor research, and researchers then noticed that some members of the series accumulate in mitochondria. SS-31 became the lead compound for mitochondrial research. A 2014 review by Szeto in the British Journal of Pharmacology describes the discovery and development of SS-31 as the first compound designed to interact with cardiolipin.

Clinical development, under the name elamipretide, has been led by Stealth BioTherapeutics. Trials have studied several conditions in which mitochondrial function is impaired.

Mechanisms studied in preclinical work

Cardiolipin binding. Cardiolipin is a phospholipid found almost only in the inner mitochondrial membrane, where it shapes the folds (cristae) and helps organise the respiratory chain. Using a fluorescent analogue, Birk et al. (2013) reported that SS-31 binds cardiolipin with high affinity.
Cytochrome c. The same work reported that the SS-31-cardiolipin complex inhibited the peroxidase activity of cytochrome c, a reaction that damages cardiolipin under stress.
Kidney ischemia model. In rats, pre-exposure to SS-31 preserved cristae structure during kidney ischemia and was associated with faster recovery of cellular ATP after blood flow returned.

These are laboratory and animal findings about mitochondrial structure and energy production.

The published research landscape

SS-31 is unusual among the compounds on this site because it has been through formal clinical development.

Primary mitochondrial myopathy. A randomised crossover trial in adults by Karaa et al. (2020) was followed by MMPOWER-3, a phase 3 randomised placebo-controlled trial reported by Karaa et al. (2023) with 218 participants. MMPOWER-3 did not meet its primary endpoints, the six-minute walk test and a fatigue score.
Barth syndrome. Barth syndrome is a rare genetic disease of cardiolipin metabolism. Smaller trials in this condition formed the basis of FDA's 2025 decision, described below.

Regulatory status

United States. On 19 September 2025, FDA granted accelerated approval to Forzinity (elamipretide) for Barth syndrome in people weighing at least 30 kg. The approval was based on knee extensor muscle strength, an intermediate endpoint, and FDA required a confirmatory randomised, placebo-controlled trial. The approval covers that prescription product only.
Research-grade material. SS-31 sold as a laboratory reagent is not Forzinity, has not been evaluated by FDA and is not covered by the approval.
Elsewhere. We found no EU marketing authorisation as of 19 October 2026.

Key terms

Cardiolipin. A phospholipid with four fatty-acid chains, found almost only in the inner mitochondrial membrane.
Cristae. The folds of the inner mitochondrial membrane, where much of the respiratory chain sits.
Accelerated approval. An FDA pathway that allows approval based on an intermediate or surrogate endpoint, with a required confirmatory trial.
Primary endpoint. The main outcome a trial is designed to test. Missing it means the trial did not show the effect it set out to measure.

Open research questions

How cardiolipin binding translates into measurable changes in tissue function in different conditions.
Whether findings in Barth syndrome, a disease of cardiolipin itself, apply to other mitochondrial disorders.
How long-term exposure affects mitochondrial membranes and cardiolipin content in animal models.

Limitations of the evidence

The phase 3 trial in primary mitochondrial myopathy did not meet its primary endpoints.
The Barth syndrome approval is conditional on a confirmatory trial.
Preclinical findings in specific injury models do not predict outcomes in other conditions.

Where researchers source it

Purita is a store that lists SS-31 for laboratory research use only. Its product page carries the label "For Research Use Only. Not for human or animal administration."

Purita product page

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