SS-31 / Elamipretide
Cardiolipin stabiliser targeting the inner mitochondrial membrane — the most advanced mitochondrial peptide in clinical research.
Research facts
| Half-life | ~2–3h |
|---|---|
| Route | SubQ / IV |
| Typical dose | 0.05–0.25 mg/kg/day |
| Frequency | Once daily SubQ |
| Solvent | Bacteriostatic water or saline |
| pH | 6.0–7.5 |
| Stability | 30 days at +4°C |
Mechanism of action
SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2) is a cell-permeable tetrapeptide that preferentially concentrates in the inner mitochondrial membrane (IMM) by binding cardiolipin — an anionic phospholipid essential for electron transport chain function and ATP synthesis. This 1,000× mitochondrial concentration is achieved via electrostatic attraction to the highly negative IMM potential.
By stabilising cardiolipin, SS-31 optimises the structure and function of electron transport chain complexes I, III, and IV. It reduces reactive oxygen species (ROS) leak from the ETC, improves ATP production efficiency, and maintains cristae morphology — the IMM folds critical for oxidative phosphorylation. In models of ischaemia-reperfusion injury, SS-31 dramatically reduces mitochondrial-mediated cell death.
Multiple Phase II/III clinical trials have evaluated SS-31 in heart failure (PROGRESS-HF), primary mitochondrial myopathy (ReCLAIM), and renal ischaemia. Results show improved mitochondrial function, reduced fatigue, and improved exercise tolerance, earning B-tier status.
Documented effects (research-model)
- Inner mitochondrial membrane cardiolipin stabilisation
- ATP production efficiency improvement
- Reduced mitochondrial ROS production
- Cardiac protection in ischaemia-reperfusion
- Reduced fatigue and improved exercise tolerance in clinical trials
- Renal protection from oxidative damage
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Standard | 0.1 mg/kg SubQ | Once daily | 12 weeks | 10mg per vial |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- NAD+ HIGH
SS-31 optimises ETC function; NAD+ provides the substrate (NADH) that ETC requires. Direct metabolic synergy. - MOTS-c HIGH
SS-31 from outer aspect of IMM; MOTS-c from mitochondrial genome. Complementary mitochondrial biogenesis + function pathways. - TB-500 MODERATE
Mitochondrial energy restoration (SS-31) + structural vascular repair (TB-500) for organ-level recovery.
Myths & misconceptions
Evidence gaps
- Phase III results in heart failure (PROGRESS-HF) showed mixed primary endpoints — efficacy in heart failure patients with preserved ejection fraction remains uncertain.
- Optimal dosing route (SubQ vs. IV) and dose-response in research contexts not fully established.
- Long-term safety beyond 12 weeks not characterised.
Safety notes
Generally well-tolerated in clinical trials. Injection site reactions reported. No serious adverse events in Phase II. Weight-based dosing important — do not exceed 0.25 mg/kg.
Biomarkers to monitor
Primary-source citations
- PMID 21693804 — SS-31 (Elamipretide) improves cardiac and skeletal muscle function in aging (J Gerontol Biol Sci. 2011)
- PMID 27040509 — Elamipretide cardioprotection in heart failure: PROGRESS-HF (JACC Heart Fail. 2016)
Frequently asked
What is SS-31 / Elamipretide?
SS-31 / Elamipretide (Szeto-Schiller Peptide 31 — Mitochondria-Targeted Cardioprotective Peptide) is a research compound classified in our library as Tier B — Some human data + strong preclinical evidence.. Cardiolipin stabiliser targeting the inner mitochondrial membrane — the most advanced mitochondrial peptide in clinical research.
What is the evidence tier for SS-31 / Elamipretide?
We classify SS-31 / Elamipretide as Tier B: Some human data + strong preclinical evidence. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of SS-31 / Elamipretide?
For SS-31 / Elamipretide, typical research dose is 0.05–0.25 mg/kg/day, route is SubQ / IV, half-life is ~2–3h. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
What does SS-31 / Elamipretide stack well with?
SS-31 / Elamipretide stacks well with NAD+. SS-31 optimises ETC function; NAD+ provides the substrate (NADH) that ETC requires. Direct metabolic synergy.
Is SS-31 / Elamipretide safe?
Generally well-tolerated in clinical trials. Injection site reactions reported. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.