SS-31

What is SS-31?

SS-31, also written SS31 and known in the clinical literature as elamipretide, MTP-131 or Bendavia, is a synthetic aromatic-cationic tetrapeptide, sequence D-Arg-Dmt-Lys-Phe-NH₂ where Dmt is 2,6-dimethyltyrosine, molecular formula C₃₂H₄₉N₉O₅, molecular weight 639.79 g/mol, CAS 736992-21-5. The alternating cationic and aromatic residues make the molecule membrane-permeant while carrying a net positive charge at physiological pH, and its defining property is where it accumulates: the peptide concentrates in the inner mitochondrial membrane and interacts with cardiolipin, the phospholipid found essentially nowhere else in the cell, as characterised by Birk and colleagues (J Am Soc Nephrol, 2013). It is one of very few compounds in this catalogue with randomised controlled human trial history (Karaa et al., Neurology, 2018), though its clinical status remains investigational after mixed Phase 3 outcomes. Supplied as lyophilised powder for in-vitro research use only, not a licensed medicine.

Why Cardiolipin Targeting Is Studied

Almost every peptide in this catalogue works through a receptor — a protein expressed on particular cell types in particular tissues. SS-31 does not. Cardiolipin, its binding partner, is a structural phospholipid confined to the inner mitochondrial membrane and present wherever mitochondria are, which means the peptide accumulates at the site of oxidative phosphorylation in essentially any cell. Birk and colleagues (J Am Soc Nephrol, 2013) showed that this cardiolipin interaction re-energised ischaemic mitochondria, improving electron transport chain function and reducing reactive oxygen species generation. That receptor-independence is what makes the compound experimentally useful: bioenergetic endpoints — respiration, membrane potential, ROS output — can be read in cardiac, renal, skeletal muscle or neuronal preparations with one and the same tool compound. It also carries a caution: because the target is ubiquitous, tissue selectivity cannot be assumed in any model, and effects must be attributed by measurement rather than by expectation. The human chapter is equally distinctive — a randomised dose-escalation trial in primary mitochondrial myopathy (Karaa et al., Neurology, 2018) followed by mixed Phase 3 SPIMM-301 outcomes — so the honest summary is a mechanistically well-characterised compound whose clinical value remains unresolved.

SS-31 Research Applications

SS-31 is used in in-vitro and animal models of mitochondrial bioenergetics: ischaemia models, isolated mitochondria and permeabilised fibre respirometry, electron transport chain efficiency and membrane potential assays, reactive oxygen species measurement, and cardiolipin-peptide interaction studies in model membranes. The foundational work is Birk and colleagues (J Am Soc Nephrol, 2013), who demonstrated that SS-31 re-energises ischaemic mitochondria by interacting with cardiolipin in the inner mitochondrial membrane. Uniquely for this catalogue, the compound also anchors a genuine clinical literature — Karaa and colleagues (Neurology, 2018) published a randomised dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy — giving researchers human pharmacology papers to read alongside bench work. The limits should be stated as plainly as the strengths: Phase 3 SPIMM-301 outcomes in mitochondrial myopathy were mixed, elamipretide is not an approved medicine anywhere, and material supplied here is for in-vitro laboratory research only.

Reconstitution Guide

Allow vials to reach room temperature, then sterilise the rubber stopper of both the peptide vial and the bacteriostatic water vial with an alcohol swab. Slowly draw your bacteriostatic water into a sterile insulin syringe, then inject it gently down the inner glass wall of the peptide vial, never directly onto the lyophilised powder. Once added, gently swirl the vial in a slow circular motion until fully dissolved. Never shake or vortex. SS-31 is a small, highly water-soluble tetrapeptide and dissolves rapidly; a clear, colourless solution should form almost immediately. Because the Dmt residue is phenolic, keep the preparation away from strong oxidisers and avoid prolonged light exposure during handling. Label the vial with the reconstitution date and store immediately.

See our full peptide reconstitution guide and reconstitution calculator for step-by-step protocol.

Storage Instructions

Lyophilised vials should be stored at -20°C, protected from light and moisture, and remain stable for up to 24 months. Once reconstituted with bacteriostatic water, store the solution at 2-8°C (standard refrigerator) and use within approximately 4 weeks. For storage beyond that, prepare single-use aliquots at -20°C. The D-configured arginine and unnatural dimethyltyrosine residues make the backbone inherently resistant to proteolysis, so oxidation of the phenolic Dmt ring is the degradation route worth designing against — store dark, minimise headspace, and avoid repeated freeze-thaw cycles. Handle under sterile laboratory conditions throughout.

Frequently Asked Questions

Research References

• The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin (Birk et al., J Am Soc Nephrol, 2013)
• Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy (Karaa et al., Neurology, 2018)

Related Research Compounds

• → MOTS-C 10mg
• → NAD+ 500mg
• → Bacteriostatic Water 10ml