SS-31 (Elamipretide)

Molecular identity

Sequence

D-Arg-Dmt-Lys-Phe-NH₂ (Dmt = 2′,6′-dimethyltyrosine; C-terminal amide)

Formula

C32H49N9O5

Molecular weight

639.8 g/mol

CAS

736992-21-5

PubChem CID

11764719

What it acts on

• Cardiolipin in the inner mitochondrial membrane — the cited reviews describe selective binding to this phospholipid as the primary molecular event, with no classical receptor involved.
• Cristae architecture and oxidative phosphorylation — binding is reported to stabilise cristae structure and to raise ATP production across the preclinical models the reviews collect.
• Mitochondrial reactive-oxygen-species production — the peptide is described as a mitochondrion-targeted antioxidant that inhibits excessive ROS formation and so lowers oxidative stress in the cited models.
• BDNF signalling and hippocampal synaptic proteins — in the cited mouse endotoxin model, treatment is reported to reverse the loss of synaptic-signalling proteins and to increase synaptic structural complexity.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewInt J Mol Sci (2025)

   A 2025 review of structure, mechanism of action and reported therapeutic potential. It attributes the mitochondrial selectivity to the peptide's unusual structure and describes cardiolipin binding as the event behind cristae stabilisation, reduced oxidative stress and increased ATP production, then summarises preclinical models of heart failure, neurodegeneration, ischaemia–reperfusion injury, metabolic syndromes and muscle atrophy. The clinical programmes (PROGRESS-HF, TAZPOWER, MMPOWER-3, ReCLAIM) are named and glossed rather than analysed, and the review closes by listing long-term efficacy and safety among the things still to be investigated.

2. 2.
   reviewDrugs (2026)

   A development-milestone summary in Drugs. It records that in September 2025 the compound received accelerated approval in the USA to improve muscle strength in adult and paediatric patients with Barth syndrome above a specified body-weight threshold — the first disease-specific approval for that ultra-rare X-linked recessive disorder — and that phase III development continues in dry age-related macular degeneration and in mitochondrial myopathies. It is a regulatory history rather than a trial report: it carries no endpoint data of its own, the approval it describes is an accelerated one, and the phase III programmes it names are unfinished.

3. 3.
   reviewHeart Fail Rev (2022)

   A 2022 review in Heart Failure Reviews focused on the cardiomyopathy of Barth syndrome, a rare X-linked disease with skeletal-muscle weakness, growth delay and cyclic neutropenia. It describes the peptide as a water-soluble aromatic-cationic tetrapeptide that penetrates cells readily and localises transiently to the inner mitochondrial membrane, and reports rapid improvement of mitochondrial bioenergetics and morphology in induced pluripotent stem cells derived from patients. Its central arguments — durability of effect after treatment stops, and gradual structural reverse remodelling of the failing left ventricle — are the authors' synthesis of data assembled across models rather than the output of one controlled study, and the review frames the field explicitly in terms of challenges as well as opportunities.

4. 4.
   animal modelJ Neuroinflammation (2019)

   The only primary study in this reference set. In mice given lipopolysaccharide to induce inflammation, the authors used the Morris water maze and contextual fear conditioning for hippocampus-related learning and memory, ELISA and molecular assays for mitochondrial function, oxidative stress and the inflammatory response, and TUNEL and Golgi staining for neural apoptosis and dendritic-spine density. Treated animals showed less mitochondrial dysfunction and oxidative stress, reversal of synaptic-signalling proteins and greater synaptic structural complexity via BDNF signalling, and better task performance. The authors state at the outset that the compound's effect on the cognitive sequelae of inflammatory and oxidative stress was unknown, and their extension to perioperative neurocognitive disorders is offered as a possibility rather than demonstrated — this is an acute rodent endotoxin model.

Used in research on