SS-31
Elamipretide / MTP-131 / Bendavia
SS-31 (Elamipretide, also known as Bendavia or MTP-131) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane where it binds to cardiolipin, stabilizing cristae structure and optimizing electron transport chain efficiency. Developed by Stealth BioTherapeutics, it represents a novel class of mitochondrial protective agents that do not rely on membrane potential for targeting. Its primary research applications include Barth syndrome, primary mitochondrial myopathy, heart failure, and age-related mitochondrial dysfunction.
Mechanism of Action
Mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane. Binds cardiolipin to optimize electron transport chain function, reduce reactive oxygen species production, and restore mitochondrial bioenergetics.
Research Protocols
For research purposes only. Not medical advice.
Clinical trial protocols used 0.25mg/kg/hour IV infusion or 40mg daily subcutaneous injection. Research protocols use 1-5mg daily subcutaneously. Treatment duration varies by indication (4 weeks to 48 weeks in trials).
Research Notes
Clinical Research Status
SS-31 (Elamipretide) has advanced through multiple Phase II and Phase III clinical trials, most notably the TAZPOWER trial for Barth syndrome and the MMPOWER trials for primary mitochondrial myopathy. The FDA granted Fast Track designation for Barth syndrome, though the compound has faced regulatory setbacks with initial NDA submissions requiring additional data. Stealth BioTherapeutics continues clinical development programs targeting heart failure with reduced ejection fraction and dry age-related macular degeneration.
Key Published Findings
In the TAZPOWER Phase II trial, elamipretide demonstrated improvements in 6-minute walk test distance and patient-reported outcomes in Barth syndrome patients over 12 weeks of subcutaneous administration. Preclinical studies have shown SS-31 reduces mitochondrial ROS production by 50-75%, improves ATP synthesis, and prevents cardiolipin peroxidation in ischemia-reperfusion models. Research in aged mice demonstrated that SS-31 treatment reversed age-related declines in skeletal muscle mitochondrial energetics and improved exercise tolerance within one hour of administration.
Safety Profile
SS-31 has demonstrated good tolerability in clinical trials at subcutaneous doses of 4mg and 40mg daily, with injection site reactions being the most common adverse event. Serious adverse events in trials have been infrequent and generally not attributed to the drug. The peptide has a favorable pharmacokinetic profile with rapid absorption, short half-life requiring daily dosing, and no evidence of accumulation or organ toxicity in long-term administration studies.
Drug Interactions & Contraindications
No significant drug-drug interactions have been identified in clinical studies to date, likely due to SS-31's mechanism of action at the mitochondrial membrane rather than via enzymatic pathways. The compound does not appear to interact with cytochrome P450 enzymes or common drug transporters. Caution may be warranted in patients taking other mitochondrial-targeted compounds, though formal interaction studies are limited.
Comparison to Related Compounds
Unlike CoQ10 and MitoQ which require mitochondrial membrane potential for uptake, SS-31 concentrates in mitochondria independent of membrane potential, making it effective even in damaged or dysfunctional mitochondria. MitoQ is a ubiquinone-based antioxidant targeting the matrix, while SS-31 specifically targets the inner membrane cardiolipin interface. SS-31's mechanism of stabilizing cardiolipin microdomains is fundamentally different from traditional antioxidants, addressing structural rather than purely redox-related mitochondrial dysfunction.
Community Observations
Research peptide users report noticeable improvements in exercise capacity and subjective energy levels within the first week of subcutaneous SS-31 administration at 2-5mg daily. The compound has gained significant interest in the longevity community due to preclinical data showing rapid reversal of age-related mitochondrial decline. Users note that SS-31 is relatively expensive and difficult to source compared to other peptides, limiting widespread adoption outside clinical trial settings.
Half-Life
~4-6 hours
Reconstitution
Bacteriostatic water (BAC)
Storage
Lyophilized
Refrigerate 2-8C. Protect from light.
Reconstituted
Refrigerate 2-8C. Use within 14 days.
US Legal Status
Also Known As
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