Journal September 17, 2026 7 min read

How to Reconstitute SS-31 (Elamipretide)

A laboratory reconstitution guide for SS-31 (elamipretide), covering its formal identifiers, the cardiolipin-binding mechanism, and the animal and clinical research that defines its handling and solubility profile.

peptides-pro Editorial

What SS-31 (Elamipretide) Is

SS-31, also known as elamipretide, is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyltyrosine). It is classified as a mitochondria-targeted therapeutic peptide, and its alternating cationic and aromatic residues give it a molecular weight of approximately 639.8 g/mol and a molecular formula of C32H49N9O5. The compound is supplied as a lyophilized powder for laboratory research use only.

The work on SS-31 centres on the mitochondrial inner membrane, specifically its interaction with cardiolipin and the electron transport chain. The peptide's aromatic-cationic motif drives its accumulation at the inner membrane, where it associates with cardiolipin and supports oxidative phosphorylation.

Research Studies

SS-31 and radiation-induced cardiomyocyte senescence

A study evaluated the effects of the mitochondrial-targeted peptide SS-31 on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Exposure to gamma-radiation at doses of 2, 5, and 10 Gy inhibited H9C2 cell proliferation in a dose-dependent manner and induced senescence-associated beta-galactosidase (SA-beta-gal) staining. SS-31 attenuated these senescence markers in the irradiated cells [1]. This work was conducted in cell culture models, not in whole animals or humans.

SS-31 and alpha-synuclein membrane binding and aggregation

Membrane binding and aggregation properties of alpha-synuclein are closely associated with Parkinson's disease and a class of related syndromes named synucleinopathies. A study explored the potential of SS-31 to modulate alpha-synuclein interaction with lipid membranes and to mitigate the impairment of mitochondrial function induced by alpha-synuclein oligomers. Using fluorescence correlation spectroscopy and fluorescence anisotropy, the researchers demonstrated that SS-31 displaces both wild-type and N-terminal acetylated alpha-synuclein from membranes [2]. This is an in vitro biophysical study; no animal or human data are reported.

SS-31 and Barth syndrome: clinical trial 4TAZPower

A Phase 3b/4, randomized, double-blind, parallel-group, placebo-controlled clinical trial is evaluating the efficacy, safety, and pharmacokinetics of a once-daily subcutaneous injection of elamipretide in subjects with genetically confirmed Barth syndrome (BTHS) for 72 weeks. The primary objective is to confirm the efficacy of elamipretide, which is approved in the United States under the brand name FORZINITY under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint [3]. This is a human clinical trial; the population is patients with genetically confirmed BTHS.

SS-31 and gestational diabetes mellitus: redox imbalance and mitochondrial dysfunction

Mitochondrial dysfunction and redox imbalance are increasingly recognised as essential factors in the pathophysiology of gestational diabetes mellitus (GDM). Impaired oxidative phosphorylation in the placenta, increased production of reactive oxygen species, and insufficient antioxidant protection impair bioenergetics and affect maternal-foetal nutrient exchange. Such changes promote excessive foetal growth and metabolic programming while predisposing mothers to future type 2 diabetes. Current research indicates alterations in mitochondrial dynamics and mitophagy as additional risk factors for placental disease [4]. This review does not report SS-31 administration; it provides context for mitochondrial-targeted research in this area.

SS-31 and healthy aging: physical function study

A clinical study is utilizing a daily dose of elamipretide for 4 weeks and will screen a sufficient number of subjects for 30 subjects to enroll. The planned duration includes baseline measurement, followed by a 4-week intervention period, a midpoint (2 weeks plus or minus 3 days) check-in phone interview, and post-intervention visits that mirror the baseline visits. After the last injection, subjects enter a 2-week follow-up period, concluded by the end-of-study contact [5]. This is a human study in healthy aging subjects; no efficacy results are reported in the registry entry.

SS-31 and expanded access for Barth syndrome

An intermediate-size expanded access protocol for elamipretide is available. Choosing to participate in an expanded access program is an important personal decision. The treating physician must contact Stealth Biotherapeutics using the Expanded Access Program Contacts provided. Elamipretide will only be made available after careful review of an individual request submitted by the treating physician. The initiation and conduct of treatment with elamipretide for an individual patient, and compliance with the treatment guideline, are under the full and sole responsibility of the treating physician [6]. This is a human expanded access program, not a controlled trial.

SS-31 and dry age-related macular degeneration: the ReNEW trial

A Phase 3 study is evaluating the efficacy, safety, and pharmacokinetics of elamipretide in subjects with dry age-related macular degeneration (AMD). The main questions it aims to answer are the rate of change in the macular area of photoreceptor loss in subjects who receive a daily dose of elamipretide compared with those who receive a look-alike substance that contains no active drug, and the safety and tolerability of elamipretide daily subcutaneous injections. Participants receive either once-daily subcutaneous doses of 40 mg elamipretide or placebo, and the two treatment groups are compared [7]. This is a human clinical trial in patients with dry AMD.

SS-31 and primary mitochondrial myopathy from nuclear DNA mutations

SPIMD-301 is a 48-week, randomized, double-blind, parallel-group, placebo-controlled trial to assess the efficacy and safety of single daily subcutaneous administration of elamipretide as a treatment for subjects with primary mitochondrial myopathy associated with nuclear DNA mutations (nPMD) [8]. This is a human clinical trial; the population is patients with nPMD.

SS-31 and MASLD in aged female mice

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a major cause of cirrhosis, liver cancer, and cardiovascular disease. Early mitochondrial dysfunction drives lipid imbalance, inflammation, and fibrosis. Given the lack of approved pharmacological treatments, a study compared the mitochondria-targeting compounds MitoQ and SS-31 in aged female mice under nutritional stress [9]. This is an animal study; no human data are reported.

SS-31 and rheumatoid arthritis: macrophage autophagy and cGAS-STING signalling

Despite decades of intensive investigation, rheumatoid arthritis (RA) remains a therapeutic challenge, primarily attributed to its intricate pathological microenvironment and poorly elucidated etiology. Mitochondrial dysfunction and abnormal activation of the cGAS-STING signalling pathway play a key role in RA. A study engineered mitochondria-targeted biomimetic hybrid nanovesicles to ameliorate RA via regulating macrophage autophagy and cGAS-STING signalling [10]. This is a preclinical study; SS-31 is referenced as a mitochondrial-targeting motif, not as a standalone therapeutic in human RA.

SS-31 and traumatic brain injury: mitochondrial oxidative stress

Traumatic brain injury (TBI) evolves through time-dependent secondary injury, but whether seawater immersion merely amplifies pathology or reshapes the temporal trajectory of post-traumatic biology remains unclear. A study applied time-resolved proteomics to mouse brains after controlled cortical impact with seawater immersion and revealed mitochondrial oxidative stress as a modifiable therapeutic target [11]. This is an animal study; no human data are reported.

SS-31 and Barth syndrome: a mitochondria-targeting drug

A review describes elamipretide as a mitochondria-targeting drug for Barth syndrome [12]. This is a review article; it does not report new primary data.

Reconstitution and Handling

SS-31 is supplied as a lyophilized powder. For laboratory reconstitution, the peptide is typically dissolved in sterile water or a suitable buffer. Because the molecule contains cationic and aromatic residues, it is generally soluble in aqueous solutions. The exact reconstitution volume depends on the desired working concentration and the assay being performed. Researchers should consult the product datasheet for specific solubility data and storage recommendations. Lyophilized powder should be stored desiccated at -20 degrees Celsius, and reconstituted solutions should be aliquoted and stored at -80 degrees Celsius to avoid repeated freeze-thaw cycles.

If you are reading this for personal health reasons

This material is sold for laboratory research use only. We do not provide dosing or medical guidance. Anyone considering a compound for themselves should speak to a licensed clinician.