Elamipretide (SS-31, MTP-131)

Elamipretide (SS-31, MTP-131) binds with high affinity to cardiolipin, an anionic phospholipid expressed on the inner mitochondrial membrane that is required for cristae formation. In addition, the complex of this compound with cardiolipin inhibits cytochrome c peroxidase activity, which catalyzes cardiolipin peroxidation and results in mitochondrial damage during ischemia, by protecting its heme iron.[1]

Intracellular targeting of Elamipretide (SS-31, MTP-131) is determined by incubating feline kidney cells, grown in biotin-free media for 24 hours, with biotinylated compound for 1 hour. Cells are then fixed with 4% paraformaldehyde, permeabilized with 0.1% triton, and treated with Streptavidin-AlexaFluor594 for 30 minutes at room temperature. Fluorescence staining is observed by wide-field fluorescent microscope.

Pretreatment of rats with Elamipretide (SS-31, MTP-131) protects cristae membranes during renal ischemia and prevents mitochondrial swelling. Prompt recovery of ATP on reperfusion leads to rapid repair of ATP-dependent processes, such as restoration of the actin cytoskeleton and cell polarity. Rapid recovery of ATP also inhibits apoptosis, protects tubular barrier function, and mitigates renal dysfunction.[1]

C₃₂H₄₉N₉O₅