SS-31 (Elamipretide)

Mitochondria-targeted tetrapeptide that stabilizes cardiolipin and restores electron transport chain function. Most advanced mitochondrial peptide in clinical trials for heart failure, Barth syndrome, and aging.

Overview

Also Known As

Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2

Mechanism of Action

Selectively concentrates 1000-fold in inner mitochondrial membrane. Binds cardiolipin, stabilizing electron transport chain. Optimizes complex III-IV electron transfer, reduces ROS, restores ATP synthesis.

Product

Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2 vial

Dosing & Administration

Typical protocols and routes

Half-Life

Approximately 4 hours

Administration Routes

subcutaneousintravenous

Dosing Protocols

Reconstitute 50 mg vial with 1 mL bacteriostatic water, giving 10 equal doses. Draw 10 units on insulin syringe (marked 1-100) for one dose.

Research

Key findings and status

Key Research Findings

TAZPOWER: improved 6-min walk in Barth syndrome. PROGRESS-HF: heart failure trial. ReCLAIM: age-related macular degeneration. Siegel et al. (2013): reversed age-related mitochondrial decline in mice.

Detailed Information

SS-31 (elamipretide, Bendavia, MTP-131) is a mitochondria-targeted tetrapeptide developed by Stealth BioTherapeutics. It selectively concentrates in the inner mitochondrial membrane at more than 1000-fold over extracellular concentrations, where it stabilizes cardiolipin and restores mitochondrial bioenergetics. SS-31 is the most advanced mitochondrial peptide in clinical development.

Mechanism of Action

SS-31 contains an alternating aromatic-cationic motif (D-Arg-Dmt-Lys-Phe-NH2) that drives its selective accumulation in mitochondria. Once there, it binds to cardiolipin — a phospholipid unique to the inner mitochondrial membrane essential for electron transport chain function. By stabilizing cardiolipin, SS-31 optimizes electron transfer between complexes III and IV, reduces electron leak and ROS production, and restores ATP synthesis capacity.

Clinical Development

SS-31 has undergone multiple clinical trials. The TAZPOWER trial in Barth syndrome (a cardiolipin-related genetic disease) showed improvements in 6-minute walk test distance. Trials in heart failure (PROGRESS-HF), age-related macular degeneration (ReCLAIM), and primary mitochondrial myopathy have been conducted. Siegel et al. (2013) showed SS-31 reversed age-related decline in mitochondrial function and improved exercise tolerance in aged mice.

Safety & Legal

Side Effects & Warnings

Injection site reactions, headache, nausea. Generally well-tolerated in clinical trials.

Legal Status

Investigational drug with orphan drug designation for Barth syndrome. Research use only.

Molecular Data

Chemical properties

Molecular Weight

639.8 g/mol

Amino Acid Sequence

D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2,6-dimethyltyrosine)