SS-31 (Elamipretide): Mitochondria-Targeted Peptide Research Guide
SS-31, known by its international nonproprietary name elamipretide, is a synthetic four-amino-acid mitochondria-targeted peptide that accumulates at the inner mitochondrial membrane and binds cardiolipin, the phospholipid that anchors the respiratory chain. Because mitochondrial energy failure sits behind a range of diseases, the molecule has been studied in Barth syndrome, primary mitochondrial myopathy and heart failure, and in September 2025 it became the first FDA-approved treatment for Barth syndrome. This page collects the published mechanism, the trial results, the ss-31 dosage ranges used in study protocols, pharmacokinetic data, and practical handling notes for lyophilised vials. It is educational reference material for laboratory and catalogue research, not medical advice.
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What Is SS-31: Molecule, Names and Product Forms
SS-31 is a tetrapeptide written as D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH2. One arginine residue sits in the D configuration, which slows enzymatic breakdown, while the alternating aromatic and cationic side chains give the molecule a net positive charge that pulls it toward negatively charged membrane surfaces. The hydrochloride salt used in medicine has the molecular formula C32H49N9O5 x 3 HCl and a molecular weight of 749.2, and it is freely soluble in water.
Several names describe the same molecule. SS-31 was the original research code, MTP-131 appeared in early cardiac programmes, Bendavia was used for cardiovascular and ophthalmic development, elamipretide is the generic name, and Forzinity is the brand of the approved injectable. Papers that use any of those labels are describing one compound.
Anyone ordering the ss-31 peptide for laboratory work should keep its identity, purity and vial size separate from the clinical data, because research specifications and pharmaceutical specifications are not the same document.
Two physical forms exist. The approved medicine is a ready-to-use aqueous solution of 80 mg/mL in single-patient-use vials. Laboratory suppliers, including the SS-31 50 mg Forzinity vial in the Dragon Pharma catalogue, ship the peptide as a lyophilised powder that has to be reconstituted before use. Concentration and storage rules differ between the two forms, so the instructions for the medicine cannot be copied onto a research vial.
Mechanism: Cardiolipin Binding at the Inner Mitochondrial Membrane
Cardiolipin is found almost exclusively in the inner mitochondrial membrane, where it supports cristae curvature, stabilises respiratory chain supercomplexes and holds cytochrome c in position. When cardiolipin is oxidised, the respiratory chain loses efficiency, electrons leak and generate more reactive oxygen species, and cytochrome c escapes into the cytosol, which triggers apoptosis. Several mitochondrial diseases, Barth syndrome among them, are rooted in abnormal cardiolipin rather than in a defective respiratory protein.
SS-31 acts on this lipid layer. Its cationic residues bind cardiolipin through electrostatic interactions, forming a complex that shields the lipid from oxidation and inhibits the cardiolipin-dependent peroxidase activity of cytochrome c. The effects reported in mechanistic studies are reduced electron leak and reactive oxygen species production, better preservation of cristae structure, and improved ATP synthesis. The FDA label summarises the same idea in one line, describing elamipretide as a mitochondrial cardiolipin binder that localises to the inner mitochondrial membrane and improves mitochondrial morphology and function.
The cardiolipin pathway also provides a measurable marker. In Barth syndrome, mutations in the TAZ gene impair tafazzin, the enzyme that remodels cardiolipin, and the ratio of monolysocardiolipin to cardiolipin (MLCL/CL) rises. In the long-term extension study of elamipretide in Barth syndrome, that ratio improved and the change correlated with clinical outcomes, which supports the view that the drug engages its intended target rather than acting as a generic antioxidant.
Research peptides that touch neighbouring parts of metabolism are often discussed alongside SS-31: MOTS-c is a mitochondrial-derived peptide studied for metabolic signalling, NAD+ 500 mg addresses a different step of cellular energy transfer, and Epitalon belongs to the research literature on peptide effects on aging markers. None of them shares the cardiolipin mechanism of SS-31.
Elamipretide in Clinical Trials: Barth Syndrome, Mitochondrial Myopathy and Heart Failure
Elamipretide has been through more than a decade of human testing. The outcomes differ sharply between indications, and the table below separates them using the numbers published in the trial reports and in the approved product label.
| Study | Population and dosing | Published outcome |
|---|---|---|
| TAZPOWER, phase 2/3 randomized crossover (Barth syndrome) | 12 patients, 40 mg subcutaneously once daily, 12 weeks per arm with a 4-week washout | Neither primary endpoint (6-minute walk test and symptom fatigue score) was met in the randomized phase |
| TAZPOWER open-label extension | 10 patients continuing 40 mg subcutaneously daily, 8 reached week 36 in the published analysis | Walk distance improved by 95.9 m at week 36 (p = 0.024); secondary endpoints included knee extensor strength, patient global impression of symptoms and several cardiac parameters |
| MMPOWER-3, phase 3 (primary mitochondrial myopathy) | 218 adults randomized 1:1, 40 mg subcutaneously daily, 24 weeks | Primary endpoints (6-minute walk test and total fatigue score) not met; baseline walk distance was 336.7 m |
| PROGRESS-HF, phase 2 (heart failure with reduced ejection fraction) | 71 patients, placebo, 4 mg or 40 mg subcutaneously daily, 28 days | No significant difference in left ventricular end-systolic volume at week 4; the drug was well tolerated |
Barth syndrome is the narrow indication that succeeded, and the reasons are worth understanding. It is an X-linked recessive disorder caused by variants in TAZ, it affects mainly males, and it begins in many patients with severe heart failure in infancy. Patients who survive into adolescence and adulthood commonly have fatigue, poor stamina and exercise intolerance, and before approval there was no licensed therapy for the condition.
In the TAZPOWER extension, function kept improving over time rather than plateauing. Reported improvements included knee extensor strength measured by handheld dynamometry, patient global impression of symptoms and several cardiac parameters, in addition to the gain in walk distance. In the approved label, the extension data appear as a median knee extensor strength change of 63 newtons at week 168, measured against a baseline median of 124 newtons in the same twelve-patient programme. The weakness of this evidence base is its size: fewer than twenty patients were treated across the controlled and open-label Barth syndrome work, which is why the approval rests on an intermediate endpoint and carries a requirement for a confirmatory trial.
In the larger indications the picture is reversed. A phase 3 trial in 218 adults with genetically confirmed primary mitochondrial myopathy showed no benefit on walk distance or fatigue after 24 weeks of 40 mg daily, and a phase 2 heart failure trial in 71 patients found no improvement in left ventricular volumes after four weeks of subcutaneous dosing. Mitochondrial dysfunction is therefore not enough on its own to predict a response; the Barth syndrome population differs because its defect sits directly in cardiolipin remodelling.
SS-31 Dosage Reported in Published Research
The ss-31 dosage that appears most often in human protocols is 40 mg subcutaneously once daily. Every figure below comes from a trial report or from the approved label, and none of them is a recommendation for self-administration.
| Regimen | Setting and notes |
|---|---|
| 40 mg subcutaneously once daily | Approved dose for patients with Barth syndrome weighing at least 30 kg; injected daily at the same time, missed doses are skipped rather than doubled |
| 20 mg subcutaneously once daily | Reduced dose for adults with an estimated glomerular filtration rate below 30 mL per minute who are not on dialysis |
| 4 mg subcutaneously once daily for 28 days | Low-dose arm of the heart failure phase 2 programme, used as a comparator against 40 mg |
| 2 to 80 mg single or daily subcutaneous doses | Dose range used to characterise pharmacokinetics; exposure rises proportionally with only minimal accumulation on repeated dosing |
The dose is organ-dependent in one specific way. Because elamipretide and its metabolites leave the body through the kidneys, exposure increases by 39 percent at a creatinine clearance of 60 to 89 mL per minute, by 75 percent at 30 to 59 mL per minute, and by 125 percent below 30 mL per minute, which is the basis for the reduced renal dose in the label. Nothing in the published work suggests a loading phase; steady exposure is achieved with daily dosing alone.
Half-Life, Pharmacokinetics and Lyophilised Vial Handling
The pharmacokinetic profile explains why once-daily dosing is used despite fast elimination. After subcutaneous injection, maximum plasma concentrations are reached in 0.5 to 1 hour, and absolute bioavailability is about 92 percent. The drug distributes through total body water with a volume of distribution near 0.5 L per kg and shows low plasma protein binding of roughly 39 percent. Elimination proceeds by sequential C-terminal degradation into an M1 tripeptide and an M2 dipeptide, both without pharmacological activity; by 48 hours after a dose, close to 100 percent of the dose is recovered in urine as parent drug or these two metabolites. There is no hepatic metabolism and no relevant interaction with CYP enzymes or major drug transporters.
The label does not state a human plasma half-life. Animal pharmacokinetic work reports an elimination half-life of roughly 2 hours in rats, dogs and monkeys, a duration the authors describe as sufficient for once-daily dosing to produce pharmacological effects in those species. In practice this means the tissue binding of the peptide at cardiolipin, not a long circulation time, is what carries the effect between injections.
Handling a lyophilised research vial is a different exercise from handling the approved solution, which is already dissolved and contains benzyl alcohol as a preservative. The general laboratory rules below follow standard handling guidance for lyophilised peptides:
- Storage of powder - keep the sealed lyophilised vial frozen below -15 degrees Celsius, protected from light and moisture, and let it reach room temperature before opening so that condensation does not form on the cake
- Solvent choice - sterile water or bacteriostatic water is used for most research peptides; a bacteriostatic diluent slows microbial growth in multi-use vials but is not suitable for every assay format
- Technique - add the solvent down the wall of the vial, then swirl gently or roll the vial until the powder dissolves; vigorous shaking introduces foam and can degrade the peptide
- Concentration arithmetic - a 50 mg vial reconstituted with 5 mL gives 10 mg/mL, and with 2.5 mL gives 20 mg/mL, against 80 mg/mL in the approved medicine; always record the final concentration on the vial
- Freeze-thaw cycles - avoid repeated freezing and thawing, which is a standard warning for both lyophilised and dissolved peptides; aliquot before freezing if a solution will be used more than once
- Liquid storage - frozen solutions are kept for a limited period, so prepare working volumes rather than storing large diluted batches
- Approved product comparison - the medicine is stored refrigerated between 2 and 8 degrees Celsius, must not be frozen, and is discarded 8 days after first opening, which shows how tight the stability limits are even for a formulated solution
Regulatory Status and Safety Profile
On 19 September 2025 the FDA granted accelerated approval to Forzinity (elamipretide) injection, the first approved treatment for Barth syndrome, for patients weighing at least 30 kg. The approval was based on improvement in knee extensor muscle strength, an intermediate endpoint the agency considered reasonably likely to predict patient benefit, and the manufacturer must run a post-approval randomized, double-blind, placebo-controlled trial to confirm that the strength change translates into real functional gain. The pathway was chosen because Barth syndrome has no approved alternatives and carries a high risk of early death, not because the functional data were conclusive.
Safety data come from the twelve male patients aged 12 to 35 years treated in the Barth syndrome programme, all of whom received 40 mg daily by subcutaneous injection:
- Injection site reactions dominate - in the placebo-controlled crossover, injection site erythema occurred in 100 percent of elamipretide periods versus 25 percent of placebo periods, induration and pruritus each in 67 percent versus 17 percent, and injection site pain in 75 percent versus 42 percent; most events were mild to moderate
- Eosinophil counts - increases in absolute eosinophil counts were frequent with treatment lasting 30 days or more, generally peaking around 90 days and returning to baseline after 6 to 12 months of continued exposure or after discontinuation, without associated clinical signs
- Benzyl alcohol - the formulated medicine contains benzyl alcohol as a preservative and must not be used in neonates; there is no approved use below 30 kg body weight
- Contraindication and overdose - serious hypersensitivity to any ingredient is a contraindication, and suspected overdose is expected to produce histamine-related signs such as falling blood pressure, managed with standard care
Three limits on the evidence should travel with any discussion of this peptide. First, the approval covers Barth syndrome only; elamipretide did not meet primary endpoints in primary mitochondrial myopathy or in stable heart failure with reduced ejection fraction, so results from the Barth syndrome programme cannot be extended to those populations. Second, the treated population is extremely small, which is exactly why a confirmatory trial is mandatory. Third, products sold through research catalogues such as the Dragon Pharma SS-31 50 mg vial are laboratory reagents and are not the approved medicine: they are not for human consumption, they carry no dosing instructions, and any information here is a summary of published studies rather than guidance for use.