Key takeaways
- SS-31 is a Szeto-Schiller peptide: a small aromatic-cationic tetrapeptide that concentrates in mitochondria.
- It binds cardiolipin, a lipid of the inner mitochondrial membrane, helping stabilise the machinery that makes ATP.
- As elamipretide, it received FDA accelerated approval in September 2025 for Barth syndrome.
In this guide
- What is SS-31?
- The cardiolipin target
- How it's thought to work
- Preclinical research
- Clinical development
- Related research
- FAQ
What is SS-31?
SS-31 is one of the Szeto-Schiller (SS) peptides, named after the researchers who developed them. Its sequence is D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2′,6′-dimethyltyrosine, and it has a molecular weight of 639.80 g/mol (CAS 736992-21-5). It's also known as elamipretide, MTP-131 and Bendavia.
Its design alternates positively charged and aromatic amino acids. This lets it cross cell membranes and accumulate at the inner mitochondrial membrane, without depending on the membrane potential that many mitochondria-targeted compounds rely on.
The cardiolipin target
Cardiolipin is a phospholipid found almost only in the inner mitochondrial membrane. It helps hold together the protein complexes of the electron transport chain and shapes the folded cristae where ATP is produced.
When cardiolipin is oxidised or depleted, electron transport becomes less efficient and leaks more electrons, producing more reactive oxygen species (ROS). That damage can feed on itself, since ROS oxidise more cardiolipin.
How SS-31 is thought to work
SS-31 binds cardiolipin selectively. Research suggests this interaction:
- helps stabilise cristae structure
- supports efficient electron transport and ATP synthesis
- reduces mitochondrial ROS production
A detailed review describes SS-31 as a first-in-class cardiolipin-protective compound (Szeto, British Journal of Pharmacology, 2014).
Preclinical research
SS-31 has been studied across many models where mitochondrial dysfunction plays a role:
- Ischaemia-reperfusion injury in the heart, kidney and brain
- Heart failure models
- Acute kidney injury
- Age-related mitochondrial decline in muscle and other tissues
Clinical development
Clinical development of elamipretide has focused on primary mitochondrial diseases. Not every trial met its goals: a phase 3 trial in primary mitochondrial myopathy did not meet its primary endpoints. In September 2025, the FDA granted elamipretide accelerated approval as the first treatment for Barth syndrome, a rare inherited disorder that directly affects cardiolipin.
The approval covers a specific pharmaceutical product for a specific rare disease. Research-grade SS-31 is a laboratory compound and is named among unauthorized peptides in Health Canada's 2026 advisory.
Related research
SS-31 is often studied alongside other mitochondrial research compounds, including MOTS-c, a mitochondrial-derived signalling peptide, and NAD+, which carries electrons to the chain SS-31 helps protect.
Frequently asked questions
What is SS-31?
SS-31 is a Szeto-Schiller tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) designed to concentrate at the inner mitochondrial membrane, where it binds cardiolipin.
Is SS-31 the same as elamipretide?
Yes. Elamipretide is SS-31's international nonproprietary name. It has also been known as MTP-131 and Bendavia.
What is cardiolipin?
Cardiolipin is a phospholipid found almost only in the inner mitochondrial membrane. It supports the electron transport chain complexes and the cristae where ATP is produced.
Is elamipretide approved?
Yes, for one indication. The FDA granted elamipretide accelerated approval in September 2025 for Barth syndrome. Research-grade SS-31 is for laboratory use only.
References
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029–2050.
