SS-31

Most peptides act through a receptor expressed on particular cell types. Cardiolipin sits in the inner membrane of every mitochondrion, so one tool compound can be used in cardiac, renal, skeletal muscle or neuronal preparations. Birk and colleagues showed the SS-31 and cardiolipin complex blocks the peroxidase activity of cytochrome c, which otherwise oxidises cardiolipin during ischaemia. In rat kidney ischaemia, pretreatment protected cristae, prevented mitochondrial swelling and sped ATP recovery on reperfusion. The same ubiquity is a caution: tissue selectivity cannot be assumed, so attribute effects by measurement.

SS-31, also written SS31 and known in the clinical literature as elamipretide, MTP-131 or Bendavia, is a synthetic aromatic-cationic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂, where Dmt is 2,6-dimethyltyrosine, a non-proteinogenic tyrosine analogue carrying methyl groups on the two ring positions flanking the phenolic hydroxyl. Its molecular formula is C₃₂H₄₉N₉O₅, molecular weight 639.79 g/mol, CAS number 736992-21-5. The alternating cationic and aromatic residues give the molecule a net positive charge at physiological pH while leaving it membrane-permeant, and the D-configured arginine together with the unnatural Dmt residue confers resistance to proteolytic degradation. Mechanistically, SS-31 is unusual in this catalogue because its target is not a receptor at all. Birk and colleagues (J Am Soc Nephrol, 2013) demonstrated that the peptide concentrates in the inner mitochondrial membrane by interacting with cardiolipin, the signature phospholipid of that membrane, and that in ischaemia models this interaction re-energised the mitochondria, improving electron transport chain function and reducing reactive oxygen species generation. Because cardiolipin is present in essentially every mitochondrion rather than in one tissue type, the compound is studied across cardiac, renal, skeletal muscle and neuronal bioenergetics models. SS-31 also has something almost no other compound in this catalogue has: genuine randomised controlled trial history. Karaa and colleagues (Neurology, 2018) published a randomised dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. The honest completion of that story is that later Phase 3 work was mixed, the SPIMM-301 trial in the same indication did not produce unambiguously positive outcomes, so elamipretide remains an investigational compound with no marketing authorisation in the UK or anywhere else. The trial record distinguishes the molecule; it does not license it. Each vial contains 50mg of SS-31 as white lyophilised powder, batch UKPL-753, recorded at 99.1% purity by RP-HPLC, certificate published on this page. Supplied strictly for in-vitro laboratory research use only.