SS-31

The Mitochondria-Targeting Tetrapeptide

SS-31 (also known as Elamipretide, Bendavia, and MTP-131) is a synthetic tetrapeptide that selectively targets the inner mitochondrial membrane. Discovered by Drs. Hazel Szeto and Peter Bhling during opioid receptor research, SS-31 represents a first-in-class therapeutic that directly addresses mitochondrial dysfunction by interacting with cardiolipin.

With multiple clinical trials completed or ongoing across heart failure, primary mitochondrial myopathy, Barth syndrome, and other conditions, SS-31 is among the most clinically advanced mitochondria-targeting peptides.

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Why Cardiolipin Targeting Matters

SS-31's interaction with cardiolipin influences mitochondrial structure and function:

Mechanism	Effect	Therapeutic Implication
Cardiolipin Binding	Stabilizes cristae structure	Preserved membrane organization
ETS Optimization	Enhances electron transport	Improved ATP production
ROS Reduction	Decreases oxidative stress	Cellular protection
Membrane Potential	Maintains proton gradient	Efficient bioenergetics

The peptide accumulates 5,000-fold in mitochondria compared to cytosol, enabling targeted therapeutic effects.

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Research Focus Areas

SS-31 is being studied for its potential effects on:

• Heart failure — left ventricular function and cardiac remodeling
• Primary mitochondrial myopathy — muscle function restoration
• Barth syndrome — cardiolipin metabolism disorders
• Ischemia-reperfusion injury — cardiac and renal protection
• Aging muscle — sarcopenia and exercise tolerance
• Neurodegenerative diseases — Alzheimer's and Parkinson's models
• Diabetic complications — nephropathy and cardiomyopathy
• Optic neuropathy — Leber's hereditary optic neuropathy

Phase 2/3 trials have shown mixed results across indications.

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Clinical Development Context

• Developer: Stealth BioTherapeutics
• Phase: Multiple Phase 2/3 trials (various indications)
• Designations: Fast Track (mitochondrial myopathy), Orphan Drug (Barth syndrome, LHON)
• Trial results: Mixed efficacy; favorable safety profile
• Regulatory status: Not FDA approved; investigational

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Technical Specifications

• Synonyms: Elamipretide, Bendavia, MTP-131
• Class: Mitochondria-targeting peptide / Cardiolipin modulator
• Sequence: D-Arg-Dmt-Lys-Phe-NH₂ (Dmt = 2',6'-dimethyltyrosine)
• Molecular Formula: C₃₂H₄₉N₉O₅
• Molecular Weight: ~639.8 g/mol
• Form: Sterile lyophilized powder or solution
• Half-life: ~1-2 hours

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Storage & Handling

• Lyophilized: Store at -20°C
• Reconstituted: Store at 2–8°C
• Protect from light and moisture
• Avoid repeated freeze-thaw cycles

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