SS-31 (Elamipretide)
A mitochondria-targeting tetrapeptide that binds cardiolipin to protect the inner mitochondrial membrane, with exceptional cardiac and anti-aging research data.
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Compound Profile
SS-31 (Elamipretide)
Key Data
Research reference only
Research Focus
Preclinical data
⚠ Research & Educational Use Only. SS-31 (Elamipretide) is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.
- Selectively targets and concentrates in the inner mitochondrial membrane - up to 1,000-fold concentration gradient in mitochondria
- Protects cardiolipin - the signature phospholipid of the inner mitochondrial membrane that is essential for electron transport chain function
- Prevents cytochrome c release - the key event initiating mitochondrial apoptosis
- SS-31 (Elamipretide) is not FDA-approved for human use. It is a research chemical for scientific study only.
Research At a Glance
- Selectively targets and concentrates in the inner mitochondrial membrane - up to 1,000-fold concentration gradient in mitochondria
- Protects cardiolipin - the signature phospholipid of the inner mitochondrial membrane that is essential for electron transport chain function
- Prevents cytochrome c release - the key event initiating mitochondrial apoptosis
- Dramatically improves cardiac function in heart failure research - Phase 2 trials showed significant improvements in cardiac output and exercise capacity
In Plain English
Simple summarySS-31 (also known as elamipretide or Bendavia) is a tetrapeptide developed specifically to target the inner mitochondrial membrane -- it has an unusual aromatic-cationic structure that allows it to concentrate in mitochondria at concentrations up to 1000-fold higher than in the surrounding cytoplasm. It binds cardiolipin, a phospholipid found almost exclusively in the inner mitochondrial membrane that's essential for the electron transport chain. By stabilizing cardiolipin, SS-31 appears to preserve mitochondrial membrane integrity, reduce electron leak (and therefore reactive oxygen species), and maintain ATP production under stress conditions. It has been studied in heart failure, ischemia-reperfusion injury, kidney disease, and aging-related mitochondrial decline.
- Selectively targets and concentrates in the inner mitochondrial membrane - up to 1,000-fold concentration gradient in mitochondria
- Protects cardiolipin - the signature phospholipid of the inner mitochondrial membrane that is essential for electron transport chain function
- Prevents cytochrome c release - the key event initiating mitochondrial apoptosis
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is SS-31 (Elamipretide)?
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SS-31 (Elamipretide, also known as MTP-131 or Bendavia) is a synthetic tetrapeptide that selectively targets and protects the inner mitochondrial membrane by stabilising cardiolipin, a phospholipid essential for electron transport chain function and ATP synthesis. It is the most clinically advanced mitochondria-targeting peptide.
What It Is
- A 4-amino acid cell-penetrating peptide (D-Arg-2'6'-dimethylTyr-Lys-Phe-NH2) containing alternating basic and aromatic residues that target it to the inner mitochondrial membrane
- Acts on cardiolipin: a unique four-tailed phospholipid exclusive to the inner mitochondrial membrane that organises the electron transport chain complexes into respiratory supercomplexes
- Does not require an active membrane potential to enter mitochondria; concentrates 1000-fold in the inner mitochondrial membrane
- In Phase 2/3 clinical trials for heart failure (PROGRESS-HF), Barth syndrome, and primary mitochondrial myopathy
How It Works
- Cardiolipin stabilisation: binds cardiolipin electrostatically (basic residues) and through aromatic interactions (dimethylTyr), preventing cardiolipin peroxidation and maintaining the curvature of cristae membranes required for efficient ATP synthesis
- ETC supercomplex maintenance: cardiolipin organises respiratory chain supercomplexes (Complex I-III-IV respirasomes); SS-31 prevents cardiolipin oxidation that disrupts these supercomplexes; example: aged heart mitochondria treated with SS-31 showed 40% recovery of supercomplex organisation (BN-PAGE)
- ATP production: restores mitochondrial membrane potential and oxygen consumption rate in aged or damaged mitochondria; example: isolated aged heart mitochondria showed 35-50% reduction in state 3 respiration vs young; SS-31 treatment restored to 85-90% of young values
- Reduced ROS: prevents cytochrome c from acquiring peroxidase activity (cardiolipin-bound cytochrome c generates ROS); SS-31 stabilises cytochrome c-cardiolipin interaction without peroxidase activation
Key Research Findings
- Aged mouse hearts: SS-31 infused ex vivo in aged mouse hearts restored mitochondrial function; in vivo 8-week SC SS-31 improved cardiac output, exercise capacity, and reversed diastolic dysfunction in 24-month-old mice
- Heart failure Phase 2 (PROGRESS-HF): SS-31 4-hour IV infusion significantly reduced BNP (heart failure biomarker) vs placebo in acute heart failure; a 4-week daily infusion trial showed improved peak VO2 and 6-minute walk distance
- Barth syndrome (rare cardiolipin disorder): SS-31 IV produced significant improvement in exercise capacity and quality of life in a Phase 2 open-label study of 12 Barth syndrome patients
- Kidney ischemia: SS-31 pre-treatment reduced AKI severity in ischaemia-reperfusion kidney models by 40-60%; mechanism involves reduced mitochondrial permeability transition pore opening
Dosing From the Literature
- Phase 2 human trials: 0.25-0.5 mg/kg IV infusion over 4 hours
- Animal studies: 3-20 mg/kg/day subcutaneous
- Currently no approved dose for clinical use outside trials
Storage and Handling
- Lyophilised: 2-8 degrees C; stable 24 months; protected from light and moisture
- Reconstituted (IV): normal saline; stable 24 hours at room temperature; use within 24 hours
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on SS-31 (Elamipretide). See all Immune System peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
Dosing Data from the Literature
Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.
SS-31 clinical trial dosing has used a range of doses depending on the indication:
For cardiac applications (EMPOWER trial in heart failure with preserved ejection fraction): 0.25 mg/kg IV infusion over 4 hours. These are hospital-administered intravenous protocols not replicable in research community settings.
For research community subcutaneous administration: 5–10 mg per injection, once or twice daily. Some researchers use 1–5 mg once daily for general mitochondrial support.
A 4-week cycle with 2-week breaks is a common protocol, though the clinical trial data suggests longer treatment periods may provide cumulative benefits. Unlike many research peptides, SS-31 does not appear to cause tachyphylaxis - efficacy is maintained with ongoing use in animal studies.
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
Reconstitute SS-31 from lyophilised powder with bacteriostatic water. For a 10 mg vial: 1 ml BAC water gives 10 mg/ml; a 5 mg dose is 0.5 ml. Administer subcutaneously via insulin syringe. The abdomen is the standard site.
SS-31 does not have food or timing requirements - it can be administered at any time. Many researchers use it in the morning as part of a longevity stack. Some use it post-workout to enhance mitochondrial recovery from exercise-induced oxidative stress.
SS-31 is relatively heat-stable for a peptide but should still be stored at 2–8°C in reconstituted form. Lyophilised powder is stable at -20°C for extended periods.
What the research doesn't show
The Phase 2 heart failure trial results were mixed -- some endpoints showed improvement, others didn't reach statistical significance. The compound is scientifically compelling (the mechanism is well-supported), but the jump from mitochondria protection in isolated cells to meaningful outcomes in heart failure patients has proven harder than expected. Clinical development continues but hasn't produced a clear efficacy signal yet.
Research Video
Medical Expert Videos
Physicians, researchers, and pharmacologists explain SS-31 (Elamipretide), covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
SS-31 (Elamipretide) has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: selectively targets and concentrates in the inner mitochondrial membrane - up to 1,000-fold concentration gradient in mitochondria.
The most commonly reported side effect in research subjects is injection site reactions - transient pain and redness with subcutaneous administration. It is a research chemical, not approved for human use.
Frequently Asked Questions
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How It Compares
MOTS-c and humanin are also mitochondria-focused peptides but work through signaling rather than direct membrane protection. CoQ10 and MitoQ are other mitochondria-targeted compounds in common use but are small molecules, not peptides, and have less membrane specificity than SS-31. Among peptide approaches, SS-31 has the most advanced clinical trial record for cardiac applications.
Compare SS-31 (Elamipretide) side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.