SS-31 (Elamipretide / Bendavia / MTP-131)
Also Known AsElamipretide · Bendavia · MTP-131 · D-Arg-Dmt-Lys-Phe-NH2
Designed by Hazel Szeto and Peter Bhatt at Weill Cornell Medical College as a cell-permeable, mitochondria-targeted tetrapeptide. The alternating aromatic-cationic motif enables selective concentration in the inner mitochondrial membrane at >1000-fold relative to extracellular concentration.
D-Arg-Dmt-Lys-Phe-NH2How SS-31 Works
Cardiolipin Interaction
Selectively binds cardiolipin on the inner mitochondrial membrane via electrostatic and hydrophobic interactions. This stabilizes cardiolipin's interaction with cytochrome c, maintaining its electron carrier function and preventing conversion to a peroxidase that generates reactive oxygen species.
Electron Transport Chain Optimization
By stabilizing the cardiolipin–cytochrome c interaction, SS-31 improves electron transfer efficiency through Complex III and Complex IV, reducing electron leak at Complex I and Complex III and thereby lowering mitochondrial superoxide production at the source.
Mitochondrial Permeability Transition Inhibition
Prevents opening of the mitochondrial permeability transition pore (mPTP) under stress conditions, preserving membrane potential (ΔΨm) and preventing release of cytochrome c and apoptosis-inducing factor into the cytosol.
Mitochondrial Dynamics
Preclinical evidence suggests modulation of mitochondrial fission/fusion balance by preserving cristae structure and supporting OPA1-mediated fusion, which maintains functional mitochondrial networks under metabolic stress.
Published Research
Cardiac Ischemia-Reperfusion Injury
StrongPhase I/II clinical trials (EMBRACE STEMI, NCT01572909) demonstrated reduced infarct size when administered during percutaneous coronary intervention. Preclinical models show preserved left ventricular function and reduced myocardial fibrosis following ischemia-reperfusion. Mechanisms include prevention of cardiolipin peroxidation and mPTP opening.
Barth Syndrome (TAFAZZIN Deficiency)
ModeratePhase II TAZPOWER trial (NCT03098797) in Barth syndrome patients showed improvements in six-minute walk test distance and cardiac stroke volume. Barth syndrome features pathological cardiolipin remodeling due to TAFAZZIN mutations, making it a direct target for SS-31's mechanism of action.
Age-Related Mitochondrial Dysfunction
ModeratePreclinical studies in aged mice demonstrate reversal of age-related decline in skeletal muscle mitochondrial energetics, improved exercise tolerance, and restoration of redox balance. SS-31 treatment in aged animals restores Complex I-linked and Complex II-linked respiration to levels approaching young controls.
Renal Ischemia-Reperfusion
PreclinicalAnimal models of acute kidney injury show protection of mitochondrial structure and function, reduced tubular necrosis, and preservation of GFR when SS-31 is administered before or shortly after ischemic insult.
Neurodegenerative Disease Models
PreclinicalPreclinical data in MPTP-induced parkinsonism and amyloid-beta toxicity models show protection of mitochondrial function and reduced neuronal death. The ability to cross the blood-brain barrier and concentrate in neuronal mitochondria supports further investigation.
Safety Profile
SS-31 has been administered in multiple Phase I and Phase II clinical trials with a generally favorable safety profile. The most commonly reported adverse events include injection site reactions and transient changes in taste perception. No dose-limiting toxicities were observed in the EMBRACE STEMI trial at doses up to 0.25 mg/kg/hr. Preclinical toxicology studies showed no mutagenicity or organ toxicity at tested doses.
Handling & Storage
Reconstitute with bacteriostatic water. SS-31 is a small, stable tetrapeptide with good aqueous solubility. Store lyophilized powder at -20°C. Reconstituted solution should be stored at 2-8°C and used within 28 days. Protect from prolonged light exposure.
Peer-Reviewed Literature
- 1
First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics
Szeto HH.
- 2
The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin
Birk AV, Liu S, Soong Y, et al.
- 3
Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice
Siegel MP, Kruse SE, Percival JM, et al.
- 4
EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention
Gibson CM, Giugliano RP, Kloner RA, et al.
- 5
A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism
Reid Thompson W, Hornby B, Manuel R, et al.
SS-31 FAQ
What is SS-31?
SS-31 (also known as Elamipretide or Bendavia) is a synthetic mitochondria-targeted tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2. It selectively concentrates in the inner mitochondrial membrane where it binds cardiolipin, stabilizing electron transport chain function and reducing oxidative stress at the source.
How does SS-31 target mitochondria?
SS-31 uses an alternating aromatic-cationic motif (positively charged and aromatic residues) that exploits the large negative membrane potential across the inner mitochondrial membrane. This drives its accumulation >1000-fold inside mitochondria without requiring any active transport or targeting sequence.
Has SS-31 been studied in human clinical trials?
Yes. SS-31 (as elamipretide) has been evaluated in multiple clinical trials including EMBRACE STEMI (cardiac ischemia-reperfusion), TAZPOWER (Barth syndrome), and studies in primary mitochondrial myopathy and age-related macular degeneration. Results have shown generally favorable safety and preliminary efficacy signals.
How should SS-31 be stored?
Lyophilized SS-31 should be stored at -20°C for long-term stability. Reconstituted solution should be kept at 2-8°C and used within 28 days. Protect from prolonged exposure to light.
SS-31 Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
SS-31
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.