SS-31

SS-31 Research Overview

SS-31 is a four-amino-acid peptide that concentrates in the inner mitochondrial membrane and binds cardiolipin, stabilizing energy production. As elamipretide it has been through multiple human trials, most notably for the rare mitochondrial disease Barth syndrome.

Also known as: Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2, Szeto-Schiller peptide 31

Background

SS-31 was designed in the early 2000s by Hazel Szeto and Peter Schiller while working on opioid peptides. They noticed that certain small peptides with alternating aromatic and basic residues accumulated in mitochondria at very high concentrations. SS-31 is one of those, built from D-arginine, a modified tyrosine, lysine, and phenylalanine. Its unnatural residues make it resistant to breakdown, and its charge pattern drives it to the inner mitochondrial membrane. Stealth BioTherapeutics licensed it and developed it as elamipretide.

It is unusual among research peptides in having a substantial human trial record. Elamipretide has been tested in heart failure, primary mitochondrial myopathy, dry age-related macular degeneration, and Barth syndrome, a rare genetic cardiolipin disorder. Results were mixed. The large mitochondrial myopathy trial missed its primary endpoint, while the small Barth syndrome program showed improvements in an open-label extension that were convincing enough that the FDA granted accelerated approval in 2025 under the brand name Forzinity after initially rejecting it. Macular degeneration results were encouraging in early phases and remain in development.

In animals SS-31 has an enormous literature: it protects the heart and kidneys from ischemia, reverses age-related decline in muscle energy production, improves mitochondrial function in old mice within hours, and reduces oxidative damage across many tissues. Gray-market SS-31 is not the pharmaceutical product and its purity varies.

Mechanistic Profile

SS-31 crosses cell membranes freely and concentrates over a thousandfold in the inner mitochondrial membrane, where it binds cardiolipin, a phospholipid unique to that membrane. Cardiolipin anchors the electron transport chain complexes and cytochrome c in the correct arrangement for efficient electron flow. When cardiolipin becomes oxidized or displaced under stress, electron transport gets leaky, ATP production falls, and reactive oxygen species rise. SS-31 binding stabilizes cardiolipin and the associated protein complexes, restoring the membrane curvature of the cristae, improving ATP output, and reducing electron leak. It also prevents cytochrome c from converting into a peroxidase that oxidizes cardiolipin and triggers apoptosis. Because it targets structure rather than scavenging radicals, it works differently from ordinary antioxidants.

Reported Research Findings

• SS-31 binds cardiolipin and restores electron transport chain efficiency in ischemic mitochondria. (in vitro)

• A single amount of SS-31 improved mitochondrial energetics and exercise tolerance in aged mice within one hour. (rodent)

• SS-31 reduced infarct size and kidney injury in rodent ischemia-reperfusion models. (rodent)

• In Barth syndrome, elamipretide improved six-minute walk distance and cardiac measures in an open-label extension after a negative crossover phase. (human RCT)

• In the large primary mitochondrial myopathy trial, elamipretide did not beat placebo on the primary walking endpoint. (human RCT)

• Elamipretide received FDA accelerated approval for Barth syndrome in 2025. (clinical (approved drug))

Analytical Validation, Formulation and Storage

• Purity: 99% or higher as verified by HPLC, with a third-party certificate of analysis available per batch.

• Formulation: lyophilised (freeze-dried) powder in a sterile sealed glass vial, to be reconstituted with an appropriate solvent for laboratory use.

• Reported half-life: Roughly 2 to 4 hours after subcutaneous injection in clinical literature (clinical data).

• Storage: keep lyophilised material cool, dark and dry (long-term at or below -20 °C). Store reconstituted solutions refrigerated, avoid repeated freeze-thaw cycles and use within laboratory-defined windows.

Selected Literature

• First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology, 2014.

• The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology, 2013.

• A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genetics in Medicine, 2021.

• Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology, 2023.

Cloud Aminos supplies SS-31 as a high-purity research material intended strictly for controlled laboratory use in vitro or in established animal models. This compound is not approved as a drug, diagnostic or dietary ingredient and is not manufactured, packaged or marketed for human consumption, self-experimentation, clinical application or any use outside properly designed and ethically approved research protocols.