Peptide Profile
SS-31
Mitochondria-Targeted Tetrapeptide / Szeto-Schiller Peptide
CLINICAL DEVELOPMENT STAGE:
Approved
SS-31 is a mitochondria-targeted tetrapeptide studied for its effects on cardiolipin stabilization, mitochondrial bioenergetics, oxidative stress modulation, and mitochondrial disease-related dysfunction.
Compound Overview
Molecular Formula
C₃₂H₄₉N₉O₅
Molecular Weight
639.8 g/mol
CAS Number
736992-21-5
Classification
Mitochondria-Targeted Tetrapeptide / Szeto-Schiller Peptide
Regulatory Status
FDA accelerated approval
Targets / Receptors
Cardiolipin binding; inner mitochondrial membrane stabilization; electron transport chain support; ATP production; oxidative stress modulation; mitochondrial bioenergetics; skeletal muscle energy metabolism
Research Focus
Mitochondrial function; cardiolipin binding; inner mitochondrial membrane stabilization; electron transport chain support; oxidative stress modulation; ATP production; cellular bioenergetics; skeletal muscle function; mitochondrial disease research
Mechanism of Action
SS-31 is a mitochondria-targeted tetrapeptide that preferentially localizes to the inner mitochondrial membrane and interacts with cardiolipin, a phospholipid that plays a central role in mitochondrial membrane structure and energy production.
By binding cardiolipin, SS-31 has been shown to help stabilize mitochondrial membrane architecture, improve electron transport chain efficiency, support ATP generation, and reduce excessive reactive oxygen species formation. Unlike many peptides, its activity is not centered on a classic cell-surface receptor. Instead, its mechanism is best described as targeting mitochondrial membrane biology and bioenergetic function.
This mechanism is especially relevant in disorders involving mitochondrial dysfunction and abnormal cardiolipin biology, which is why elamipretide was ultimately developed most successfully in Barth syndrome.
Research Evidence
SS-31 has a substantial preclinical literature showing effects on mitochondrial function, oxidative stress, bioenergetics, and tissue protection across multiple organ systems. Mechanistic studies strongly support its cardiolipin-directed mitochondrial activity.
Human clinical evidence is more mixed and indication-specific. In Barth syndrome, a phase 2/3 clinical trial followed by an open-label extension reported improvements in several functional outcomes over longer-term treatment. This development pathway ultimately led to FDA accelerated approval in 2025 as Forzinity for improvement of muscle strength in patients with Barth syndrome weighing at least 30 kg.
By contrast, broader mitochondrial indications have not all produced positive confirmatory results. In primary mitochondrial myopathy, the MMPOWER-3 phase 3 trial reported that elamipretide did not significantly improve the primary functional endpoints at 24 weeks versus placebo. This makes SS-31 a good example of a peptide with a strong mechanism, mixed broader clinical outcomes, and one narrow FDA-approved indication rather than a universally proven mitochondrial therapy.
Safety & Limitations
SS-31 is now FDA approved in a narrow indication, but that does not mean it is broadly validated for all mitochondrial, longevity, or recovery-related uses. Its approved use is specifically tied to Barth syndrome in patients meeting the labeled criteria.
Outside that approved indication, the evidence base is more limited and mixed. Some clinical programs have shown encouraging findings, while others, including a phase 3 study in primary mitochondrial myopathy, failed to meet key efficacy endpoints. This means broader claims should be made cautiously.
The most commonly reported adverse events in clinical trials were injection-site reactions, which were generally mild to moderate. Serious reactions have also been reported. Long-term benefits and risks outside the approved indication remain less well established than many marketing claims suggest.
Key References
- Birk AV, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology. 2013.
- Thompson WR, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genetics in Medicine. 2021.
- Karaa A, et al. The MMPOWER-3 Randomized Clinical Trial: Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy. Neurology. 2023.
- Thompson WR, et al. 168-week open-label extension results of TAZPOWER. Molecular Genetics and Metabolism. 2024.
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. FDA. 2025.
Last scientifically reviewed: September 4, 2026
