SS-31, known generically as elamipretide (development codes MTP-131, Bendavia), is a synthetic, cell-permeable tetrapeptide that selectively accumulates at the inner mitochondrial membrane and binds the phospholipid cardiolipin.1 It has been studied more extensively in humans than most research peptides: it progressed through several randomized controlled trials in primary mitochondrial myopathy, dry age-related macular degeneration, heart failure and Barth syndrome.23 Importantly, most of these trials did not meet their primary efficacy endpoints. In September 2025 the developer’s hydrochloride salt formulation (brand name Forzinity) received accelerated FDA approval to improve muscle strength in Barth syndrome on the basis of an intermediate endpoint, even though the pivotal trial was not superior to placebo on its co-primary endpoints; a confirmatory trial is required.4 The material sold by research-chemical suppliers is the unapproved free-base or acetate peptide, supplied for research use only. The information below describes what has been reported in published studies and does not constitute usage directions.
Sequence & identity
H-D-Arg-Dmt-Lys-Phe-NH₂ · C₃₂H₄₉N₉O₅ · 639.8 g/mol
Chemical identity verified against PubChem (CID 11764719); InChIKey SFVLTCAESLKEHH-WKAQUBQDSA-N. The molecule is a four-residue peptide amide (D-arginine, 2′,6′-dimethyltyrosine, L-lysine and L-phenylalanine amide) carrying a net positive charge that drives its accumulation at the negatively charged inner mitochondrial membrane.1
Mechanisms studied
SS-31 carries a net positive charge and crosses the plasma membrane in an energy-independent manner, then concentrates several thousand-fold at the inner mitochondrial membrane, where it binds reversibly to cardiolipin — an anionic phospholipid largely unique to that membrane.1 Researchers have reported that, by associating with cardiolipin, the peptide helps preserve cristae architecture and the assembly of electron-transport-chain supercomplexes, and reduces cytochrome-c peroxidase activity and reactive oxygen species in stressed cell and animal models, with associated improvements in ATP synthesis.1 Barth syndrome, the approved indication for the hydrochloride form, is caused by tafazzin (TAFAZZIN) mutations that lower mature cardiolipin, providing the mechanistic rationale for a cardiolipin-binding agent.4
Dosing in the research literature
The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.
| Source / model | Regimen reported | Notes |
|---|---|---|
| FORZINITY (elamipretide HCl) FDA prescribing information, 2025 | 40 mg once daily by subcutaneous injection in adults and children weighing ≥30 kg with Barth syndrome | Reported for the approved hydrochloride product only; approval was accelerated and based on an intermediate endpoint. Stated here as published, not as guidance.4 |
| MMPOWER-3 RCT, Karaa et al., Neurology 2023 | 40 mg subcutaneous once daily for 24 weeks in primary mitochondrial myopathy | Co-primary endpoints (6-minute walk distance and PMMSA Total Fatigue Score) were not statistically significant versus placebo.2 |
| ReCLAIM-2 phase 2 RCT, dry age-related macular degeneration, Ophthalmology Science 2024 | 40 mg subcutaneous once daily for 48 weeks | Primary endpoints (low-luminance BCVA and geographic-atrophy area) were not met; some secondary ellipsoid-zone measures favored treatment.3 |
Effects observed in research
In preclinical and cell models, studies have reported that SS-31 lowers mitochondrial reactive oxygen species, helps maintain membrane potential and supports ATP production under stress.1 Human results have been mixed. The phase 3 MMPOWER-3 trial in primary mitochondrial myopathy did not meet its co-primary endpoints, although a post-hoc subgroup with mtDNA-maintenance disorders showed a signal that prompted a follow-up trial.2 The ReCLAIM-2 trial in dry AMD likewise missed its primary endpoints while showing some favorable secondary imaging measures.3 In the pivotal Barth syndrome study the peptide was not superior to placebo on its co-primary endpoints; reported improvement in knee-extensor strength came from an open-label extension and served as the intermediate basis for accelerated approval.4 The most commonly reported adverse events across trials were mild-to-moderate injection-site reactions.4
Strength of evidence
Evidence is graded B: unlike most research peptides, elamipretide has multiple completed randomized controlled human trials, but the majority of pivotal efficacy endpoints were not met, and the single accelerated approval rests on an intermediate endpoint with a confirmatory trial still required.4 Mechanistic and preclinical support for cardiolipin binding is strong;1 robust clinical efficacy across the broader conditions studied remains unproven.23
Reconstitution & storage
Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.
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. PMID 24117165.
- Karaa A, Bertini E, Carelli V, et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252.
- Allingham MJ, et al. ReCLAIM-2: A Randomized Phase 2 Clinical Trial Evaluating Elamipretide in Age-Related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. Ophthalmol Sci. 2024.
- FORZINITY (elamipretide) injection, prescribing information; U.S. FDA accelerated approval, NDA 215244, September 19, 2025; and FDA press announcement, ‘FDA Grants Accelerated Approval to First Treatment for Barth Syndrome.’