Overview
A mitochondria-targeted tetrapeptide that binds cardiolipin on the inner mitochondrial membrane. It has progressed further into human clinical evaluation than most research peptides in the longevity space.
Mechanism of Action
SS-31 is a four-amino-acid peptide with an alternating aromatic-cationic structure that allows it to concentrate in the inner mitochondrial membrane independent of membrane potential.
It binds cardiolipin, a phospholipid unique to the inner mitochondrial membrane that is required for the proper organisation of the electron transport chain.
By stabilising cardiolipin interactions, published work reports improved electron transport efficiency and reduced production of reactive oxygen species.
Downstream effects reported include preservation of ATP synthesis and reduced mitochondrial permeability transition under stress conditions.
Areas Being Studied
- Mitochondrial myopathy
- Cardiac and renal ischaemia research
- Skeletal muscle function in ageing
- Neurodegenerative and ophthalmic research
Listing a research area does not imply efficacy, approval, or suitability for any use.
Research Summary
- Elamipretide has been evaluated in registered human clinical trials, including studies in primary mitochondrial myopathy and Barth syndrome, with published results across several endpoints.
- Ageing research in animals reports restored mitochondrial function and improved muscle performance following administration.
- Cardiac research reports reduced infarct size in ischaemia-reperfusion models, though translation to human outcome trials has produced mixed results.
- It is one of the few peptides in this category with a substantive registered human trial record.
Potential Adverse Effects Reported in Research
- Injection-site reactions were the most frequently reported events in published human trials, sometimes leading to discontinuation.
- Gastrointestinal effects including nausea and diarrhoea were reported.
- Headache and dizziness appear in trial safety summaries.
- Long-term safety data continues to accumulate through ongoing programmes.
Reconstitution Basics
Supplied as a lyophilised powder in low-milligram vials; research protocols commonly use daily subcutaneous administration.
Bacteriostatic water
Sterile water containing roughly 0.9% benzyl alcohol as a preservative, which inhibits bacterial growth in multi-access vials.
Sterile technique
Laboratory documentation describes disinfecting the stopper, using a fresh sterile needle for each access, and avoiding contact with non-sterile surfaces.
After reconstitution
Solutions are refrigerated, protected from light, and not subjected to repeated freeze–thaw cycles.
This section is educational background on laboratory handling. It is not an instruction or protocol.
Open the reconstitution calculator →Dosing & Reconstitution Guide
SS-31 (elamipretide) has been evaluated in registered clinical trials using daily subcutaneous administration at fixed doses rather than escalating ladders.
Protocol overview
- Once-daily subcutaneous administration with site rotation is the pattern used in registered trials.
- Injection-site reactions were the most frequently reported finding and drove site rotation requirements.
- Elamipretide remains investigational and is not approved for general use.
Dosing protocol — standard titration
| Phase | Reported dose | Notes |
|---|---|---|
| Weeks 1–2 | Low fixed daily doseTrial run-in phase. | Trial run-in phase. |
| Weeks 3–12 | Target daily doseFixed dosing throughout the study period. | Fixed dosing throughout the study period. |
| Extension | Continued daily dosingOpen-label extensions ran for months in some trials. | Open-label extensions ran for months in some trials. |
Dosing protocol — gradual titration
| Phase | Reported dose | Notes |
|---|---|---|
| Week 1 | Every other day at the low doseInjection-site tolerability observation. | Injection-site tolerability observation. |
| Weeks 2–4 | Daily at the low doseGradual entry to daily schedule. | Gradual entry to daily schedule. |
| Weeks 5+ | Daily at the target doseMatches the trial maintenance pattern. | Matches the trial maintenance pattern. |
Schedules summarise what appears in published studies, trial protocols or manufacturer documentation. They are reference material, not a recommendation.
Where to Buy Compounds & Supplies
External link. PepDex does not sell products and does not endorse any supplier.
Supplies needed
Lyophilised peptide vial
Sealed vial with an intact stopper and a legible mass label (mg or mcg).
Bacteriostatic water
Sterile water with ~0.9% benzyl alcohol, used where a vial will be accessed more than once. Sterile water for injection is used for single-access work.
Reconstitution syringe
A 1–3 mL syringe with a larger-gauge needle for drawing and transferring solvent.
Insulin syringe (U-100)
Fine-gauge syringe graduated in units; 100 units = 1 mL. Used for accurate small-volume measurement.
Alcohol prep pads
70% isopropyl swabs for disinfecting both vial stoppers before every access.
Sharps container
Rigid, puncture-resistant container for single-use needle disposal.
Refrigeration and light protection
2–8 °C storage plus an opaque box or the original carton for reconstituted vials.
Labels
Date of reconstitution, resulting concentration and compound name on every vial.
Reconstitution steps
- 01
Bring the vial to room temperature
Lyophilised powder is allowed to equilibrate out of the refrigerator before the stopper is pierced, which reduces condensation inside the vial.
- 02
Disinfect both stoppers
The peptide vial and the bacteriostatic water vial are each swabbed with 70% isopropyl alcohol and allowed to air dry.
- 03
Draw the calculated solvent volume
Solvent volume is chosen to produce a convenient concentration — the reconstitution calculator converts vial mass and solvent volume into concentration and syringe units.
- 04
Add the solvent slowly down the vial wall
The stream is directed against the glass rather than onto the powder cake. Peptides are shear-sensitive and direct jetting is avoided.
- 05
Dissolve without shaking
The vial is left to stand, then gently swirled or rolled. Shaking introduces foam and mechanical stress that can denature peptide chains.
- 06
Inspect the solution
Documentation describes checking for a clear, particle-free solution. Cloudiness, visible particulate or discolouration is treated as a failed preparation.
- 07
Label and refrigerate
The vial is labelled with compound, concentration and date, then stored at 2–8 °C protected from light.
Storage instructions
- Before reconstitution: lyophilised powder is kept sealed, dry and away from light; most suppliers specify refrigeration at 2–8 °C, with freezer storage for long-term holding.
- After reconstitution: refrigerated at 2–8 °C and used within the window described in the literature (commonly cited as ~28 days refrigerated).
- Protection from light: the vial is kept in its carton or an opaque container; repeated exposure to daylight is avoided.
- Handling: repeated freeze–thaw cycles are avoided, and vials are not left at room temperature between accesses.
- Integrity checks: any solution that becomes cloudy, discoloured or shows particulate is discarded rather than filtered.
Half-Life
~2 hours
Plasma half-life is short, but mitochondrial accumulation means tissue effects are reported to persist beyond plasma clearance.
Storage
- Before reconstitution
- Lyophilised powder stored refrigerated or frozen.
- After reconstitution
- Refrigerated at 2–8 °C after reconstitution.
- Light protection
- Protected from light.
- Shelf-life considerations
- Generally described as usable for weeks refrigerated.
Frequently Asked Questions
References
- Elamipretide in patients with primary mitochondrial myopathy
Neurology, 2018
- Cardiolipin-targeted peptide SS-31 and mitochondrial function
Annual Review of Pharmacology and Toxicology
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Educational reference only. Figures are compiled from published research literature. PepDex does not provide medical advice, dosing recommendations, or instructions for use.