SS-31
Elamipretide · MTP-131 · Bendavia · SS-31 (Szeto-Schiller)
40 mg/day SC; MMPOWER-3 Phase 3 missed its 6-minute-walk primary endpoint
Overview
SS-31 (elamipretide; also known as MTP-131 and by the development name Bendavia) is one of the Szeto–Schiller peptides — a short, cell-permeable tetrapeptide engineered to concentrate selectively at the inner mitochondrial membrane. Unlike most of the longevity peptides catalogued here, it is not a fringe research chemical: it has been carried through a substantial clinical program in primary mitochondrial myopathy, Barth syndrome, heart failure, and dry age-related macular degeneration.
Its defining feature is target selectivity. The peptide binds the phospholipid cardiolipin, which is found almost exclusively in the inner mitochondrial membrane, and in doing so is proposed to stabilize the cristae folds, protect the electron-transport-chain supercomplexes, and reduce the leakage of reactive oxygen species. The rationale is to restore mitochondrial efficiency in tissues where it has failed, which is why the clinical focus has been on energy-demanding tissues such as skeletal muscle, heart, and retina.
The clinical record is genuinely mixed, and the page reflects that candidly. The pivotal Phase 3 MMPOWER-3 trial (40 mg/day subcutaneously for 24 weeks) did not meet its 6-minute-walk-test primary endpoint, though a prespecified subgroup with nuclear-DNA mutations did improve, and the ReCLAIM-2 trial in geographic atrophy likewise missed its co-primary endpoints while showing signals on some secondary visual-function measures. Because it has been studied in humans, the dosing below reflects the actual trial regimen rather than community guesswork, but it remains investigational.
Key parameters
- Dose range
- 40 mg once daily subcutaneously in trials
- Frequency
- Once daily (clinical-trial schedule)
- Half-life
- Short (a few hours by subcutaneous route)
- Route
- Subcutaneous
- Vial sizes
- 10 mg · 50 mg
- Regulatory status
- Investigational mitochondria-targeted peptide (developed by Stealth BioTherapeutics); evaluated in multiple registered human trials but not approved by the FDA or other regulators as of 2026.
Mechanism of action
Cardiolipin binding / inner-membrane stabilization
Elamipretide associates with cardiolipin in the inner mitochondrial membrane, helping preserve cristae architecture and the assembly of electron-transport-chain supercomplexes, which supports efficient ATP synthesis.
Reduction of mitochondrial oxidative stress
By stabilizing the membrane and improving electron flow, it is reported to reduce the leak of reactive oxygen species from the respiratory chain, lowering oxidative damage under mitochondrial stress.
Restoration of bioenergetic capacity
In diseased or aged tissue with impaired mitochondria, the net proposed effect is improved oxygen consumption and energy output, which underlies its testing in muscle-, heart-, and retina-related conditions.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Clinical-trial dose | Continuous in trials (e.g. 24–48 weeks) | 40 mg once daily, subcutaneous | The dose used across MMPOWER-2/3 and ReCLAIM-2. Earlier MMPOWER work also used intravenous infusion (0.25 mg/kg/h) in an acute setting. |
| Lower research-use doses | Variable | Smaller subcutaneous amounts (e.g. 5–10 mg) | Seen in research-use planning below the trial dose; not a studied regimen for efficacy. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
50 mg vial + 1 mL bacteriostatic water
Concentration50,000 mcg/mL · 50 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 10,000 mcg | 0.2 mL | 20 |
| 40,000 mcg | 0.8 mL | 80 |
Concentrated mix from a 50 mg vial that keeps the 40 mg trial dose to a single sub-milliliter draw.
10 mg vial + 2 mL bacteriostatic water
Concentration5,000 mcg/mL · 5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 5,000 mcg | 1 mL | 100 |
| 10,000 mcg | 2 mL | 200 |
Lower-strength mix from a 10 mg vial for smaller research-use doses.
Reconstitution calculator
Pre-filled with SS-31's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 10,000 micrograms per millilitre, a 10,000 microgram dose is 1 millilitres, or 100 units on a U-100 syringe, giving 1 doses per vial.
This draw is 100 units, which won't fit in a 50-unit syringe. Use more bacteriostatic water (lower concentration) or split the dose.
Supplies needed
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Recommended supply
SS-31 — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
As an investigational agent there is no approved-label missed-dose rule. On a once-daily schedule a missed dose is generally taken the same day if remembered, or otherwise skipped, without doubling up the next day.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Injection site | Injection-site erythema (redness)Injection-site reactions were the most common adverse events across the MMPOWER program; erythema was reported in a majority of treated subjects in the earlier MMPOWER study, more often than placebo. | — |
| Injection site | Injection-site itching, pain, or swellingPruritus, pain, and urticaria at the injection site were also frequent; most reactions were mild to moderate. | — |
| Neurological | Headache or dizzinessReported as less common, mild-to-moderate events in trials. | — |
| Gastrointestinal | Nausea or abdominal pain | — |
| General | Fatigue | — |
Clinical trials & evidence
MMPOWER-3
Phase 324 weeks · 218 adults with genetically confirmed primary mitochondrial myopathy
Did not meet the primary endpoint: difference in 6-minute-walk distance was −3.2 m vs placebo (95% CI −18.7 to 12.3; p=0.69). A prespecified nuclear-DNA-mutation subgroup did show improvement.
NCT03323749 ↗ReCLAIM-2
Phase 248 weeks · Adults (≥55 y) with dry AMD and noncentral geographic atrophy
Missed its co-primary endpoints (low-luminance visual acuity and GA growth) but reported signals on some secondary visual-function measures.
NCT03891875 ↗MMPOWER-2 (crossover)
Phase 24 weeks per arm · 30 adults with primary mitochondrial myopathy
40 mg/day subcutaneous produced a clinically meaningful but not statistically significant change in 6-minute-walk distance versus placebo.
Trial identifier needs verification
Storage & handling
- Lyophilized
- Refrigerate lyophilized powder at 2–8 °C, protected from light; for long-term storage a freezer (around −20 °C) is preferred.
- Reconstituted
- Refrigerate the reconstituted solution at 2–8 °C and use within roughly 28 days; do not freeze.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| MOTS-c | Inner-membrane / cardiolipin vs mitochondrial peptide signaling | Short vs not characterized | 40 mg/day SC (trials) vs 2–3× weekly (community) | SS-31 has reached Phase 3 (mixed results); MOTS-c is preclinical/community | Both not approved |
| Humanin | Cardiolipin stabilization vs mitokine/anti-apoptotic signaling | Short (both) | Daily SC in trials vs community SC | SS-31 is clinically tested; humanin is preclinical | Both not approved |
Sources & references
- [1]Karaa A et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology 2023;101(3):e238–e252. ↗ source
- [2]Allen RS et al. / Stealth BioTherapeutics. ReCLAIM-2: A Randomized Phase 2 Trial of Elamipretide in AMD-associated Geographic Atrophy. Ophthalmol Sci 2024. ↗ source
- [3]Review: Elamipretide — structure, mechanism of action, and therapeutic potential. PMC 2025. ↗ source
Frequently asked questions
What does 'mitochondria-targeted' mean for SS-31?
SS-31 is designed to accumulate at the inner mitochondrial membrane, where it binds the lipid cardiolipin. That targeting concentrates the peptide exactly where the electron-transport chain operates, which distinguishes it from general antioxidants that act diffusely throughout the cell.
Did elamipretide work in its clinical trials?
The results are mixed. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy did not meet its primary 6-minute-walk endpoint, and the ReCLAIM-2 eye trial missed its co-primary endpoints, although both reported some favorable signals in subgroups or secondary measures. It remains investigational and is not approved.
How is SS-31 dosed in studies?
The subcutaneous trials used 40 mg once daily; an earlier study used a short intravenous infusion. Because these are actual trial regimens rather than community estimates, the dosing here is better grounded than for most peptides in this category, but it is still not an approved protocol.
Related protocols
MOTS-c
Mitochondrial-derived peptide
Mitochondrial-derived peptide regulating metabolic homeostasis (preclinical)
Humanin
HN
Cytoprotective mitochondrial-derived peptide; preclinical evidence with no human RCTs
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For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.