Also known as: Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2
Half-life: ~4 hours
SS-31, also known as elamipretide, is a synthetic cell-permeable tetrapeptide that selectively targets and concentrates within the inner mitochondrial membrane. Its unique alternating aromatic-cationic motif (D-Arg-Dmt-Lys-Phe-NH2) enables it to cross cell membranes without requiring active transport and accumulate at the mitochondrial inner membrane at concentrations 1000-5000 fold higher than in the cytoplasm. There, it binds to cardiolipin, a phospholipid essential for the structural integrity of the electron transport chain.
By stabilizing cardiolipin and preventing its peroxidation, SS-31 optimizes electron transport chain efficiency, reduces electron leak, and decreases mitochondrial reactive oxygen species (ROS) production. This is fundamentally different from conventional antioxidants, which scavenge ROS after they are produced. SS-31 addresses the source of mitochondrial dysfunction rather than its downstream consequences. This mechanism has shown benefit in models of heart failure, kidney injury, neurodegenerative disease, and age-related mitochondrial decline.
Clinical development by Stealth BioTherapeutics (now Larimar Therapeutics) has advanced SS-31 through multiple Phase 2 and Phase 3 trials, including studies in Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration. While the FDA declined approval for Barth syndrome in 2023 citing insufficient efficacy data, the compound demonstrated a favorable safety profile across all clinical programs and remains in active development.
SS-31 was developed by Dr. Hazel Szeto at Weill Cornell Medical College in New York in the early 2000s. The "SS" stands for "Szeto-Schiller" after its co-developers. The peptide was designed using a structural motif (alternating aromatic and basic amino acids) that enables mitochondrial targeting. It was the first compound demonstrated to selectively concentrate in mitochondria at the inner membrane, binding to cardiolipin. Stealth BioTherapeutics (now Larimar Therapeutics) licensed the compound as elamipretide and advanced it through multiple clinical trials for mitochondrial diseases including Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration. The FDA declined to approve it for Barth syndrome in 2023, requesting additional efficacy data. Despite this setback, the peptide remains in active clinical development.
SS-31 has been evaluated in multiple clinical trials, providing reasonable human safety data. In Phase 1/2 trials, the most common side effects were injection site reactions, mild headache, and transient flushing. The peptide's extreme selectivity for mitochondrial inner membrane means it has minimal off-target effects on other cellular compartments. In the Barth syndrome trials (TAZPOWER), the treatment was generally well tolerated over extended treatment periods. The main limitation in the clinical program was demonstrating efficacy rather than safety concerns. Long-term safety data in healthy aging populations is still limited.
Dose Range
5-50 mg
Frequency
Once daily (SubQ)
Duration
4-12 weeks
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
5 mg
Water Type
Sterile water or bacteriostatic water
Mixing Volume
2 mL
Half-Life
~4 hours
Molecular Weight
639.8 Da
Store reconstituted vial refrigerated at 2-8°C. Use within 21 days. SS-31 is a small, stable tetrapeptide that maintains potency well in solution.
FDA Status
Not FDA approved. FDA declined approval for Barth syndrome in 2023, requesting additional efficacy data. Multiple clinical trials ongoing for other mitochondrial indications.
Legal Status
Investigational drug in the USA and EU. Available as a research chemical. Not scheduled or controlled.
USA
Not approvedFDA declined approval for Barth syndrome 2023, clinical trials ongoing
EU
Not approvedInvestigational status
UK
Not approvedNot evaluated by MHRA
Australia
Not approvedNot evaluated by TGA
Russia
Not approvedNot authorized
Canada
Not approvedNot authorized by Health Canada
Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH
Journal of Biological Chemistry (2004)
Foundational study demonstrating that SS-31 selectively targets mitochondria and inhibits oxidative damage, establishing the mechanism for its protective effects.
View Study →Thompson WR, Hornby B, Manuel R, Bradley E, Laux J, Carr J, Vernon HJ
Genetics in Medicine (2021)
First-in-human clinical trial of elamipretide in Barth syndrome patients showing safety, tolerability, and preliminary evidence of improved cardiac and functional outcomes.
View Study →Dai DF, Hsieh EJ, Chen T, Menber LG, Chin MT, Keller GM, Rabinovitch PS
Journal of the American Heart Association (2013)
Demonstrated that SS-31 reverses age-related mitochondrial dysfunction in the heart, restoring cardiac function and reducing oxidative stress in aged mice.
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