SS-31 (Elamipretide)

Research-Grade

SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH₂), developed under the drug name Elamipretide (trade name Elampretide), is a synthetic tetrapeptide designed by Dr. Hazel Szeto to selectively concentrate in the inner mitochondrial membrane. Its alternating aromatic-cationic motif allows it to cross cell membranes independently of mitochondrial membrane potential and accumulate at the cardiolipin-rich regions of the inner membrane within minutes of exposure. Cardiolipin is a phospholipid critical for the structural organization of the electron transport chain (ETC). Age-related oxidation of cardiolipin disrupts ETC supercomplex assembly, increases electron leak (generating reactive oxygen species), and impairs ATP production. SS-31 binds cardiolipin through electrostatic interactions between its cationic residues and the anionic phospholipid head groups, stabilizing the lipid against peroxidation and maintaining ETC efficiency. In clinical trials, Elamipretide has been evaluated in Barth syndrome (a genetic cardiolipin remodeling deficiency), primary mitochondrial myopathy, heart failure with reduced ejection fraction, and age-related macular degeneration (dry AMD). The TAZPOWER trial in Barth syndrome showed improvements in six-minute walk test distance. Phase 2 trials in heart failure showed improved left ventricular function. The MMPOWER-3 pivotal trial in primary mitochondrial myopathy did not meet its primary endpoint but showed trends in patient-reported outcomes. SS-31 represents a mechanistically novel approach — rather than supplementing downstream metabolites (like CoQ10 or NAD+), it addresses the structural platform on which oxidative phosphorylation is organized.