SS-31
Animal-onlyElamipretide · MTP-131 · Bendavia · D-Arg-Dmt-Lys-Phe-NH2
Limited evidence: the strongest curated study is Animal-only; no human-trial data found as of 2026-06-04.
Chemical & identity
- Molecular formula
- C32H49N9O5
- Molecular weight
- 639.8 g/mol · PubChem
- PubChem CID
- 11764719 · PubChem
- SMILES
- CC1=CC(=CC(=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N)NC(=O)[C@@H](CCCN=C(N)N)N)C)O
- InChIKey
- SFVLTCAESLKEHH-WKAQUBQDSA-N
- ChEMBL ID
- CHEMBL3833370 · ChEMBL
- Category
- Mitochondrial
Chemical/structural fields are auto-pulled and source-linked. ChEMBL data: ChEMBL_36, CC BY-SA 3.0.
Mechanism (curated)
Mitochondria-targeted tetrapeptide that binds cardiolipin on the inner mitochondrial membrane, stabilizing cristae and improving electron-transport efficiency while reducing reactive oxygen species. Therapeutic data are preclinical/investigational.
Pharmacology & handling
- Half-life
- Short plasma half-life; administered subcutaneously in clinical studies.
Research
Tung C et al. · International journal of molecular sciences · 2025 · Narrative review
Elamipretide (SS-31) is a mitochondria-targeting tetrapeptide that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing cristae structure, reducing oxidative stress, and enhancing ATP production. Preclinical studies have demonstrated protective and restorative efficacy in models of heart failure, neurodegeneration, ischemia-reperfusion injury, metabolic syndromes, and muscle atrophy. Clinical trials including PROGRESS-HF, TAZPOWER, MMPOWER-3, and ReCLAIM have been conducted to evaluate its therapeutic potential. This is a narrative review synthesizing current knowledge of Elamipretide's structure, mechanisms of action, and therapeutic role in mitochondrial dysfunction.
Zhao W et al. · Journal of neuroinflammation · 2019 · Animal study
This animal study (mice) investigated whether elamipretide (SS-31), a mitochondrion-targeted antioxidant, could reverse learning and memory impairment induced by lipopolysaccharide (LPS). Mice treated with LPS showed mitochondrial dysfunction, oxidative stress, neuroinflammation, neural cell apoptosis, and dendritic spine loss in the hippocampus, along with impaired performance on memory tests. Treatment with elamipretide significantly improved memory performance and reduced mitochondrial dysfunction, oxidative stress, and markers of apoptosis; it also enhanced BDNF signaling and synaptic structural complexity. The authors conclude that elamipretide may have therapeutic potential for preventing cognitive damage from oxidative stress and neuroinflammation in perioperative neurocognitive disorders.
Miyamoto S et al. · The Journal of biological chemistry · 2020 · Animal study
This study examined how elamipretide (MTP-131/SS-31), a mitochondrial protectant, affects diabetic kidney disease in db/db mice, a type 2 diabetes model. The researchers found that 18-week-old db/db mice had reduced renal and cardiac superoxide levels and increased albuminuria and mesangial matrix accumulation. MTP-131 administration significantly inhibited albuminuria, urinary hydrogen peroxide, and mesangial matrix accumulation, while preserving renal superoxide production. The drug also reduced lysocardiolipin levels and preserved lysocardiolipin acyltransferase 1 expression, suggesting protection against diabetic kidney disease may occur through regulating cardiolipin remodeling.
Patai R et al. · GeroScience · 2025 · Animal study
This preclinical study evaluated SS-31 (elamipretide), a mitochondrial-targeted antioxidative peptide, as a potential protective agent against cerebral microhemorrhages (CMHs) in an aged, hypertensive mouse model. The researchers hypothesized that mitochondrial oxidative stress contributes to age-related CMH susceptibility. Although SS-31 treatment did not significantly reduce CMH burden in the treated mice, the study developed and validated a high-throughput, machine learning-driven imaging pipeline using random forest algorithms to detect and quantify CMHs with improved accuracy and reduced processing time compared to manual counting and traditional approaches. The authors conclude that multi-targeted interventions may be necessary to address CMH-related neurovascular impairment and prevent vascular cognitive impairment and dementia, and that their imaging methodology provides a scalable platform for future preclinical therapeutic screening.
Stefaniak E et al. · Chemical biology & drug design · 2026 · In-vitro study
This study investigated SS-31 (Elamipretide), a tetrapeptide with mitochondrial-targeting and antioxidant properties, for its ability to modulate α-synuclein behavior and restore mitochondrial function. Using fluorescence correlation spectroscopy and anisotropy, the researchers demonstrated that SS-31 displaces both wild-type and N-terminal acetylated α-synuclein from negatively charged lipid vesicles in a dose-dependent manner. Thioflavin-T assay and transmission electron microscopy showed SS-31 inhibits membrane-induced α-synuclein aggregation and alters fibril morphology. In neuroblastoma cells treated with α-synuclein oligomers, SS-31 enhanced cell viability and restored mitochondrial function as measured by MTT assay and Seahorse Mito Stress Test. Confocal imaging indicated SS-31 reduces cellular uptake of α-synuclein oligomers, possibly by altering cell membrane electrostatics.
Song Z et al. · Neurochemistry international · 2026 · Animal study
Elamipretide (SS-31), a mitochondria-targeting peptide, was investigated in a mouse thoracic contusion spinal cord injury model, where it significantly enhanced locomotor recovery and gait performance while reducing lesion pathology and preserving neurons. Early after injury, SS-31 attenuated apoptosis signaling through reduced cleaved caspase-3 and Bax and increased Bcl-2; chronically, it diminished astrogliosis and enhanced axonal and synaptic remodeling markers. In oxidatively stressed PC12 cells, SS-31 preserved mitochondrial membrane potential, reduced ROS accumulation, and supported oxidative phosphorylation-related protein integrity. The study suggests SS-31 promotes recovery after spinal cord injury through mitigation of early apoptotic injury and support of mitochondrial homeostasis and neural remodeling.
Vieira Neto E et al. · Journal of inherited metabolic disease · 2026 · Other
Elamipretide, a synthetic cardiolipin-binding peptide, was tested in βTFP-deficient mice and patient-derived fibroblasts to determine whether it could improve mitochondrial function in mitochondrial trifunctional protein (TFP) deficiency, an inherited disorder of long-chain fatty acid β-oxidation. In mice treated with elamipretide via osmotic minipump, exercise endurance improved and liver mitochondria showed enhanced FAO-ETC enzyme activities, though cardiolipin content and composition remained unchanged. In patient-derived fibroblasts, elamipretide produced a possible genotype-dependent increase in mitochondrial bioenergetics and reduction in ROS. The authors propose that elamipretide stabilizes interactions between FAO enzymes and ETC complexes, improving mitochondrial function independently of cardiolipin level changes, and suggest it warrants further preclinical study as a potential therapeutic agent for TFP/LCHAD deficiency.
Birk AV et al. · Journal of the American Society of Nephrology : JASN · 2013 · Animal study
SS-31 is a mitochondria-targeted compound that binds with high affinity to cardiolipin on the inner mitochondrial membrane. In rat models of renal ischemia, SS-31 protected cristae membranes, inhibited cytochrome c peroxidase activity, prevented mitochondrial swelling, and accelerated ATP recovery on reperfusion. These effects led to rapid restoration of ATP-dependent processes, inhibition of apoptosis, and reduced acute kidney injury. The abstract notes SS-31 is currently in clinical trials for ischemia-reperfusion injury.
Jacob N et al. · Molecular genetics and metabolism · 2025 · Case report/series
Barth syndrome is a rare X-linked mitochondrial disease caused by TAZ gene variants, leading to cardiolipin defects and clinical features including cardiomyopathy, cyclic neutropenia, skeletal myopathy, and growth delay. This case report describes a prenatally identified infant with severe left ventricle non-compaction cardiomyopathy who was treated with elamipretide (ss-31) shortly after birth; the treatment was associated with significant and sustained clinical improvement, resulting in removal from the heart transplant list. The abstract notes that elamipretide has been shown in pre-clinical and clinical studies to stabilize cardiolipin and improve mitochondrial bioenergetics. No FDA-approved therapies currently exist for Barth syndrome.
Ortmann L, Velasco D, Cole J · European heart journal. Case reports · 2025 · Case report/series
This is a case report of a newborn with Barth syndrome (BTHS), a rare genetic disease causing mitochondrial dysfunction, who was treated with elamipretide (ss-31), an investigational drug that binds cardiolipin on the inner mitochondrial membrane. The patient presented at birth with a severely dilated left ventricle (LVEF 20%) and was started on elamipretide at day of life 34 at doses of 0.25–0.5 mg/kg intravenously, followed by subcutaneous dosing. Serial echocardiograms showed improvement in left ventricular ejection fraction to near-normal and eventually 60%, and the patient was discharged on day 61 on subcutaneous elamipretide and oral heart failure medications. The authors suggest elamipretide may have contributed to the improvement in left ventricular function in this BTHS infant.
Zhang H et al. · 2026 · Animal study
This study examined elamipretide, a peptide therapy, for reversing age-related decline in female fertility. The abstract reports that elamipretide improved aged human oocyte maturation and fertilization in vitro, increased litter size in aged mice, and improved oocyte quality. Mechanistic analyses suggested the peptide works via activation of the Vitamin B6-VEGF axis and improved both nuclear and cytoplasmic maturation, mitochondrial metabolism, and organelle rearrangement. The study combined human in-vitro data, mouse in-vivo data, and porcine in-vitro data, though the explicit study design and methods are not detailed in the abstract.
Nickel AG et al. · Cell metabolism · 2015 · Animal study
This animal study in mice demonstrates that mitochondrial transhydrogenase (Nnt) reversal during pressure overload generates reactive oxygen species (ROS) and contributes to heart failure. The researchers found that in C57BL/6J mice with an Nnt gene mutation, this ROS source is absent, providing protection from oxidative stress and heart failure. Treatment with the tetrapeptide SS-31 rescued mortality in pressure overload-induced heart failure in wild-type mice, suggesting potential therapeutic value.
Zhao K et al. · Biochemical pharmacology · 2005 · In-vitro study
This in-vitro study examined SS-31, a cell-penetrating, mitochondria-targeted peptide antioxidant (D-Arg-Dmt-Lys-Phe-NH2), in two neuronal cell lines (N2A and SH-SY5Y). Treatment with the oxidant tert-butyl hydroperoxide induced mitochondrial depolarization, increased ROS production, and apoptosis; concurrent treatment with <1 nM SS-31 significantly decreased intracellular ROS, restored mitochondrial potential, and prevented apoptosis. SS-31 achieved these effects through extensive cellular uptake and selective mitochondrial partitioning (6-fold higher intracellular than extracellular concentration; ~5000-fold concentration in isolated mitochondrial pellets). The authors propose SS-31 as a novel mitochondria-targeted antioxidant platform with potential therapeutic applications.
Swain L et al. · Circulation · 2024 · Other
This study investigates how venoarterial extracorporeal membrane oxygenation (VA-ECMO) promotes myocardial injury in acute myocardial infarction by depleting cardiolipin, a mitochondrial phospholipid. The research examined cardiolipin and tafazzin levels in human subjects with heart failure requiring VA-ECMO and in swine models exposed to VA-ECMO and ischemia/reperfusion injury. Results showed that VA-ECMO reduced cardiolipin and tafazzin levels in both human left ventricles and swine hearts, and increased infarct size in a swine ischemia/reperfusion model. Treatment with MTP-131, an amphipathic molecule that stabilizes the inner mitochondrial membrane by interacting with cardiolipin, reduced infarct size and restored cardiolipin levels and mitochondrial function. The authors conclude that cardiolipin is a therapeutic target to reduce myocardial injury in VA-ECMO-supported acute myocardial infarction.
Summaries are our own; we link to originals (PubMed / DOI) and never rehost full text.
Regulatory status
- FDA approved
- No
- WADA prohibited
- No
- Compounding status
- Not an approved drug; investigational (studied for Barth syndrome and primary mitochondrial myopathy).
- Notes
- Not FDA-approved as of 2026-06-04; investigational (elamipretide, studied for Barth syndrome and primary mitochondrial myopathy). Not listed on the WADA prohibited list.
Legal/regulatory status varies by jurisdiction and changes over time — accurate as of last review (2026-06-04).
Data sources: Curated IDs (PubChem/UniProt/ChEMBL) + Europe PMC + ClinicalTrials.gov (2026-06-04).
Last reviewed 2026-06-04