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SS-31 (Elamipretide)

SS-31, also known as Elamipretide, is a synthetic tetrapeptide (Dimethyltyrosine-D-Arginine-Dimethyltyrosine-Lysine-NH2) specifically designed to target mitochondrial dysfunction through selective binding to cardiolipin, a unique phospholipid found exclusively in the inner mitochondrial membrane. Originally developed as a mitochondria-penetrating peptide, SS-31 represents a novel therapeutic approach addressing fundamental cellular energetic dysfunction underlying numerous age-related diseases and pathological conditions.

This peptide has gained considerable attention in mitochondrial medicine due to its demonstrated ability to stabilize cardiolipin, optimize electron transport chain organization, and enhance cellular energy production in preclinical and clinical studies. SS-31 exhibits selective mitochondrial accumulation and maintains bioactivity through its unique cationic structure, making it distinctive among therapeutic peptides targeting cellular energetics.

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Overview

SS-31 demonstrates excellent water solubility and selective mitochondrial uptake due to its cationic properties. The peptide's unique structure enables penetration of mitochondrial membranes and selective accumulation within mitochondria based on concentration gradients and tissue mitochondrial density. It is eliminated primarily through renal excretion with minimal hepatic metabolism.

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Chemical structure & Properties

  • Molecular Formula: C20H32N8O5
  • Molecular Weight: 464.52 Da
  • Sequence: Dimethyltyrosine-D-Arginine-Dimethyltyrosine-Lysine-NH2
  • Half-life: 1-2 hours (plasma elimination)
  • Stability: Stable peptide structure with enhanced membrane penetration properties

Mechanism of Action

SS-31 exerts its therapeutic effects through highly specific mitochondrial targeting and cardiolipin stabilization:

Selective Mitochondrial Targeting and Accumulation

SS-31's unique structure enables selective mitochondrial localization through:

  • Cationic properties facilitating mitochondrial membrane penetration and accumulation
  • Selective binding to the inner mitochondrial membrane based on electrical gradient
  • Tissue-specific uptake proportional to mitochondrial density and metabolic demand
  • Concentration gradients favoring mitochondrial accumulation over cytoplasmic distribution

Cardiolipin Stabilization and Protection

The peptide's primary mechanism involves direct cardiolipin interaction:

  • High-affinity binding to cardiolipin molecules preventing peroxidation and degradation
  • Stabilization of cardiolipin structure maintaining optimal mitochondrial membrane integrity
  • Prevention of cardiolipin loss during oxidative stress and pathological conditions
  • Maintenance of cardiolipin-protein interactions essential for respiratory complex function

Electron Transport Chain Optimization

Through cardiolipin stabilization, SS-31 enhances mitochondrial respiratory efficiency:

  • Improved organization and stability of respiratory complexes I, III, and IV
  • Enhanced electron transport chain supercomplex formation and electron transfer efficiency
  • Reduced electron leakage and subsequent reactive oxygen species production
  • Optimized ATP synthesis through improved respiratory complex organization

Cytochrome C Oxidase Enhancement and Complex IV Function

SS-31 specifically targets and optimizes cytochrome c oxidase activity:

  • Direct interaction with Complex IV enhancing enzymatic activity and stability
  • Improved oxygen utilization efficiency reducing cellular oxygen requirements
  • Enhanced cytochrome c oxidase assembly and maintenance of proper function
  • Reduced oxidative stress generation through improved respiratory complex efficiency

Clinical Applications and

Research Evidence

Cardiovascular Protection and Cardiac Function

Cardiac Mitochondrial Dysfunction: Clinical studies demonstrate SS-31's efficacy in:

  • Significant enhancement in cardiac function in Barth syndrome and heart failure models
  • Improved mitochondrial morphology and enhanced ATP production in cardiomyocytes
  • Decreased apoptotic markers and enhanced cardiomyocyte survival under stress conditions
  • Preservation of cardiac tissue integrity during ischemic and oxidative stress conditions

Mechanism: Direct cardiolipin stabilization in cardiac mitochondria, improved respiratory complex organization, and enhanced cellular energy production supporting cardiac contractile function.

Renal Protection and Function Enhancement

Kidney Disease Treatment: Research indicates significant benefits in:

  • Effective protection against oxidative stress-induced renal mitochondrial damage
  • Significant reductions in serum creatinine and blood urea nitrogen levels
  • Reduced kidney tissue inflammation, fibrosis, and histopathological damage
  • Enhanced renal ATP production and improved cellular energy status

Mechanism: Mitochondrial protection in renal tubular cells, reduced oxidative stress generation, and improved cellular energy production supporting renal function and recovery.

Neurological Protection and Cognitive Enhancement

Neuroprotective Applications: Preclinical evidence supports potential benefits in:

  • Enhanced neuronal mitochondrial function and energy production
  • Protection against neurodegenerative processes and oxidative neuronal damage
  • Improved cognitive function through optimized brain cellular energetics
  • Enhanced neuroprotection during stroke and ischemic brain injury

Mechanism: Neuronal mitochondrial optimization, reduced oxidative stress in brain tissue, and enhanced cellular energy production supporting neuronal survival and function.

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Current Clinical Evidence

Safety Profile and Considerations

Preclinical Safety Data

Studies across multiple species and models demonstrate:

  • Exceptional safety profile with minimal adverse effects reported
  • No significant systemic toxicity or major organ dysfunction
  • Well-tolerated across various dosing regimens and administration routes
  • No evidence of tolerance development or diminishing therapeutic response

Reported Side Effects

Minimal and Transient Effects:

  • Rare mild injection site reactions with subcutaneous administration
  • Occasional mild fatigue during initial treatment period (uncommon)
  • No significant systemic adverse reactions or organ toxicity
  • Excellent long-term tolerability in extended treatment protocols

Potential Concerns

Theoretical Considerations:

  • Limited human clinical experience requiring careful monitoring during initial use
  • Potential interactions with medications affecting mitochondrial function
  • Individual variability in mitochondrial targeting and therapeutic response
  • Unknown effects in patients with severe mitochondrial genetic disorders

Mitochondrial Enhancement Considerations:

  • Theoretical concerns about enhanced cellular energy in malignant conditions
  • Need for careful evaluation in patients with active cancer
  • Monitoring requirements for patients with complex mitochondrial diseases

Contraindications

SS-31 should be avoided in:

  • Active malignancy or history of mitochondrial-sensitive tumors (theoretical concern)
  • Pregnancy and breastfeeding (insufficient safety data in these populations)
  • Known hypersensitivity to peptides or components of the formulation
  • Severe acute illness requiring intensive care monitoring

Regulatory Status and

Legal Considerations

Clinical Development Status

  • Classification: Investigational drug in clinical development
  • Approval Status: Not approved for routine therapeutic use
  • Clinical Trials: Multiple ongoing studies for various indications
  • Regulatory Position: Investigational new drug (IND) status for clinical research

Research Applications

  • Academic Studies: Extensive use in mitochondrial research protocols
  • Clinical Trials: Available through approved research protocols
  • Orphan Drug Status: Designated for certain rare mitochondrial diseases

Legal Availability

  • Commercial Status: Not available as prescription medication
  • Research Access: Available through clinical trial participation
  • Quality Control: Manufacturing under clinical trial standards
  • Clinical Use: Limited to approved research and clinical trial settings

Administration and Dosing

Considerations

The Paragon Method: Step-by-Step

Administration Routes

  • Intravenous infusion: Maximum bioavailability for acute mitochondrial dysfunction
  • Subcutaneous injection: Convenient outpatient administration with excellent absorption
  • Timing considerations: Can be administered any time of day
  • Monitoring requirements: Regular assessment of energy levels and clinical response

Clinical Considerations

Important Guidelines:

  • Medical supervision essential due to investigational status
  • Individual response assessment and dose optimization required
  • Integration with comprehensive mitochondrial evaluation protocols
  • Quality verification important for clinical research applications

Priority Research Areas

Clinical Development:

  • Large-scale randomized controlled trials for various mitochondrial diseases
  • Dose optimization studies for different clinical conditions and patient populations
  • Long-term safety evaluation in human clinical use
  • Biomarker development for mitochondrial function assessment and treatment response

Mechanistic Studies:

  • Detailed characterization of cardiolipin interaction mechanisms
  • Investigation of tissue-specific mitochondrial targeting and accumulation patterns
  • Combination therapy protocols with other mitochondrial-supporting agents
  • Precision medicine approaches based on individual mitochondrial function profiles

Emerging Applications

Research is investigating potential applications in:

  • Neurodegenerative diseases including Alzheimer's and Parkinson's disease
  • Age-related muscle wasting and sarcopenia
  • Diabetic complications and metabolic dysfunction
  • Exercise performance enhancement and recovery optimization
  • Longevity medicine and healthspan extension
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Conclusion

SS-31 represents a groundbreaking advancement in mitochondrial medicine, offering targeted therapeutic intervention for fundamental cellular energetic dysfunction underlying numerous diseases and aging processes. Its unique mechanism of cardiolipin stabilization and mitochondrial optimization provides unprecedented therapeutic potential across diverse medical applications.

The substantial preclinical evidence demonstrates SS-31's therapeutic efficacy in cardiovascular, renal, and neurological applications with an exceptional safety profile. However, the current evidence base remains predominantly preclinical, requiring comprehensive human clinical trials for regulatory approval and clinical implementation.

Healthcare providers should approach SS-31 with understanding of its investigational status and the need for appropriate clinical trial participation or research protocols. The peptide's innovative mitochondrial targeting mechanism and proven preclinical efficacy position it as a promising therapeutic tool for conditions rooted in mitochondrial dysfunction.

Future clinical development will be critical in establishing SS-31's role in human medicine and optimizing treatment protocols for various mitochondrial-related conditions under appropriate medical oversight.

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TB-500 SCIENTIFIC

DATA SUMMARY

MOLECULAR CHARACTERISTICS
PRECLINICAL EFFICACY DATA
CLINICAL EVIDENCE SUMMARY
SAFETY PROFILE
REGULATORY STATUS
Parameter
Molecular Weight
Amino Acid Length
Half-Life
Bioavailability
Detection Window
Value
464.52 Da
4 residues (tetrapeptide)
~1-2 hours (plasma)
Selective mitochondrial accumulation
Up to 4 hours (tissue)
Application
Wound Healing
Muscle Recovery
Tendon/Ligament
Cardiovascular
Studies
15+ studies
12+ studies
20+ studies
30+ studies
Dose Range
1-40 mg daily
5-10 mg daily
100 mcg-10 mg
100 mcg-5 mg
Outcome
Improved cardiac function, enhanced ATP production
Reduced creatinine/BUN, mitochondrial protection
Enhanced neuronal energy, neuroprotection
Cardiolipin stabilization, optimized ETC
Study Type
Renal Protection Study
Cardiac Function Trial
Mitochondrial Study
Population
Animal kidney disease models
Barth syndrome mouse model
Various dysfunction models
Results
Reduced injury markers, improved function
Enhanced cardiac function, reduced apoptosis
Improved ATP, reduced oxidative stress
Limitations
Preclinical data only
Animal study, human validation needed
Predominantly preclinical evidence
Parameter
Acute Toxicity
Organ Toxicity
Adverse Events
Long-term Safety
Finding
Exceptional safety up to 40 mg tested
No systemic toxicity or organ dysfunction
Minimal: rare injection site reactions, mild fatigue
Well-tolerated in extended protocols
Authority
FDA
WADA
Orphan Drug
Classification
Investigational Drug
Research compound
Designated status
Status
Clinical development, IND status
Not specifically prohibited
For rare mitochondrial diseases

Disclaimer: This information is provided for educational purposes only and does not constitute medical advice. SS-31 is an investigational drug not approved for routine therapeutic use. Patients interested in SS-31 should consult with qualified healthcare providers about clinical trial opportunities.

The content reflects current scientific literature and regulatory status as of 2025.