SS-31 10MG
$48.00MG
SS-31 is a mitochondria-targeted tetrapeptide being researched for its potential to support cellular energy, muscle performance, recovery, and resilience to oxidative stress. By interacting with cardiolipin in the inner mitochondrial membrane, SS-31 may help stabilize mitochondrial structure, support more efficient ATP production, and protect cells from oxidative damage. Research has explored its potential applications in healthy aging, cardiovascular and kidney protection, muscle function, and mitochondrial recovery following cellular stress. Supplied as a lyophilized powder for research purposes.
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Overview
Think of SS-31 as your mitochondria’s personal bodyguard—a specialized tetrapeptide engineered to penetrate deep into your cellular power plants and protect them from the inside out. Just as a skilled security guard positions themselves at the most vulnerable entry points, SS-31 targets cardiolipin, a critical phospholipid in the inner mitochondrial membrane, stabilizing the very architecture that keeps your cells producing energy efficiently.
Also known as Elamipretide or Bendavia, SS-31 represents one of the most exciting advances in mitochondrial-targeted therapeutics. This compact four-amino-acid peptide (D-Arg-Dmt-Lys-Phe-NH₂) has captured the attention of researchers worldwide for its remarkable ability to cross mitochondrial membranes and concentrate precisely where oxidative damage occurs most. Unlike broad-spectrum antioxidants that work throughout the cell, SS-31 acts with surgical precision at the mitochondrial level.
What makes SS-31 particularly fascinating is its mechanism—it doesn’t just neutralize free radicals like conventional antioxidants. Instead, it stabilizes the electron transport chain itself, reducing the production of reactive oxygen species at their source while simultaneously enhancing ATP production. This dual action of protection and performance enhancement has made it a compelling subject of research in cardiovascular disease, aging, kidney protection, and neurodegenerative conditions.
Key Characteristics
MOLECULAR PROFILE
- Formula: C32H49N9O5
- Weight: 639.8 g/mol
- CAS: 736992-21-5
- Sequence: D-Arg-Dmt-Lys-Phe-NH₂
PHYSICAL PROPERTIES
- Form: White to off-white lyophilized powder
- Solubility: Water-soluble
- Storage: Keep refrigerated 36‑46 °F (2‑8 °C)
- Stability: Stable when properly stored
How It Works
SS-31 operates like a precision tool for mitochondrial maintenance, concentrating 1,000 to 5,000-fold within mitochondria due to electrostatic attraction between its positively charged amino acids and the negatively charged cardiolipin in the inner membrane. This targeted accumulation allows it to protect the electron transport chain from oxidative damage while enhancing energy production efficiency.
Primary Mechanisms
Cardiolipin Stabilization
Binds directly to cardiolipin via electrostatic interactions, preventing oxidative damage to this essential phospholipid and maintaining cristae structure—the folds in the inner mitochondrial membrane where energy production occurs.
Electron Transport Chain Optimization
Interacts with key proteins in the oxidative phosphorylation pathway including Complex III, Complex IV, and ATP synthase, enhancing electron transfer efficiency and reducing electron leakage that would otherwise generate harmful reactive oxygen species.
Cytochrome C Modulation
Inhibits the peroxidase activity of cytochrome c, preventing it from contributing to oxidative stress while maintaining its essential role in the electron transport chain.
Secondary Effects
ATP Production Enhancement
By improving mitochondrial coupling efficiency (P/O ratio), SS-31 enables more ATP to be produced per unit of oxygen consumed, restoring aged mitochondria to more youthful function levels.
Oxidative Stress Reduction
Decreases mitochondrial ROS production at the source rather than scavenging free radicals after they form, representing a fundamentally different approach to antioxidant protection.
Membrane Potential Preservation
Helps maintain healthy mitochondrial membrane potential, which is essential for proper ATP synthesis and cellular signaling.
Research Findings
Laboratory and clinical investigations have revealed multiple areas where SS-31 demonstrates significant therapeutic potential, from cardiovascular protection to healthy aging support.
Cardiovascular Protection
Multiple studies demonstrate significant cardioprotective effects in various models of heart disease.
- Improves cardiac function in heart failure models
- Reduces ischemia-reperfusion injury in cardiac tissue
- Attenuates age-associated protein modifications in heart (2021)
- Restores cardiac mitochondrial morphology in Barth syndrome models (2024)
- Improves ADP sensitivity through adenine nucleotide translocator (2023)
Skeletal Muscle & Exercise Performance
Research shows remarkable improvements in aged muscle function and exercise capacity.
- Single treatment restores mitochondrial energetics to young levels in aged mice
- 8 weeks treatment reverses age-related decline in ATP production
- Improved treadmill endurance and fatigue resistance
- Restored redox homeostasis in aged skeletal muscle
- Partial preservation of muscle mass in aging models
Renal Protection
Clinical and preclinical studies show kidney-protective effects, particularly during ischemic events.
- Phase 2a trial: Attenuated post-procedural kidney hypoxia during stent revascularization
- Increased renal blood flow and improved kidney function
- Reduced kidney injury in ischemia-reperfusion models
- Accelerated ATP recovery in renal tissue after injury
Neuroprotective Properties
Emerging research suggests protective effects on brain cells and cognitive function.
- Ameliorates memory impairment in neuroinflammation models (2019)
- Regulates BDNF signaling pathways
- Reverses synaptic-signaling protein changes
- Protects against cerebral microhemorrhage in aged models (2024)
- Reduces neuroinflammation markers
Barth Syndrome Research
FDA-approved indication based on extensive clinical trial data in this rare mitochondrial disorder.
- TAZPOWER trial: 12-patient Phase 2/3 randomized clinical trial with 168-week extension
- Significant improvements in 6-minute walk test
- Increased cardiac stroke volume over long-term treatment
- Improved knee extensor muscle strength
- FDA accelerated approval granted September 2025
Structural & Pharmacological Insights
Receptor Binding Modes
Cryo-electron microscopy structures reveal GLP2-T engages both GIPR and GLP-1R through their orthosteric binding pockets in the N-terminal extracellular domain. The C20 fatty acid modification does not directly contact the receptor but positions the peptide for enhanced G protein coupling efficiency.
Transmembrane Domain Conformations
Active-state receptor structures demonstrate GLP2-T stabilizes outward movement of transmembrane helix 6, creating Gs binding interface geometry. The bias toward cAMP signaling at GLP-1R correlates with reduced conformational changes in intracellular loop 3, limiting β-arrestin recruitment.
Islet Synergy Mechanisms
Co-infusion studies demonstrate GIP + GLP-1 produce supraadditive insulin secretion (>2x individual effects). GLP2-T recapitulates this synergy in single-molecule format. Mechanistically, parallel cAMP generation from both receptors amplifies PKA-dependent phosphorylation of KATP channels and voltage-gated calcium channels, maximizing glucose-stimulated insulin secretion.
GIPR Requirement for Efficacy
Genetic ablation studies in human islets confirm GLP2-T’s insulinotropic actions require functional GIPR. In GIPR knockout models, GLP2-T loses ~60% of glucose-lowering capacity, demonstrating GIP signaling is non-redundant despite GLP-1R activation.
Potential Side Effects in Research
Clinical trials have reported a generally favorable safety profile for SS-31, with most adverse events being mild and transient. However, as with any research compound, careful monitoring is essential.
Injection Site Reactions
Most common adverse effect in clinical studies including pruritus (39%), pain (28%), erythema (19%), induration (14%), and bruising (13%)—typically mild and self-limiting
Long-term Considerations
Limited long-term data beyond clinical trial durations; extended studies (168 weeks) in Barth syndrome patients showed sustained tolerability
Systemic Effects
Occasional reports of mild headache, dizziness, and gastrointestinal effects such as nausea, flatulence, or abdominal discomfort
Dose Tolerance
Well-tolerated as IV infusion over wide dose range (0.01–0.25 mg/kg/h over 4 hours) and as subcutaneous injection (4–40 mg daily for 28 days) in human trials
References
- Tung C, et al. Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential. Int J Mol Sci. 2025.
- Thompson WR, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024.
- Pharaoh G, et al. The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT). Geroscience. 2023.
- Whitson JA, et al. Elamipretide (SS-31) treatment attenuates age-associated post-translational modifications of heart proteins. Geroscience. 2021.
- Chavez JD, et al. Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci U S A. 2020.
- Mitchell W, et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem. 2020.
- Zhao W, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation. 2019.
- Campbell MD, et al. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 2019.
- Saad A, et al. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circ Cardiovasc Interv. 2017.
- 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. Genet Med. 2021.
- Siegel MP, et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013.
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