SS-31 (Elamipretide)
Mitochondria-Targeted PeptideinvestigationalAlso known as: Elamipretide, Bendavia, MTP-131, SS-31 Peptide
A mitochondria-targeted tetrapeptide that concentrates in the inner mitochondrial membrane, protecting cardiolipin and restoring bioenergetics in aging and disease.
Overview
SS-31 (Elamipretide) is a synthetic cell-permeable tetrapeptide specifically designed to target and accumulate in the inner mitochondrial membrane. Developed by Hazel Szeto at Weill Cornell Medicine, SS-31 selectively binds to cardiolipin — a phospholipid essential for cristae structure, electron transport chain efficiency, and ATP production. By stabilizing cardiolipin and preventing its oxidation, SS-31 restores mitochondrial function, reduces reactive oxygen species (ROS) production at the source, and improves cellular bioenergetics. SS-31 has been investigated in clinical trials for Barth syndrome (a cardiolipin-deficiency disorder), heart failure, age-related mitochondrial dysfunction, and primary mitochondrial myopathy. Although it received FDA Fast Track designation for Barth syndrome, clinical trial results have been mixed, and it has not yet achieved regulatory approval. It remains one of the most scientifically rigorous approaches to targeting mitochondrial dysfunction in aging.
Mechanism of Action
SS-31 operates through direct mitochondrial membrane targeting: (1) Its alternating aromatic-cationic motif (D-Arg-dimethylTyr-Lys-Phe) allows rapid cell penetration and 1000-5000x concentration in the inner mitochondrial membrane; (2) Binds specifically to cardiolipin, stabilizing its interaction with cytochrome c and the electron transport chain complexes; (3) Prevents cardiolipin peroxidation, which is a primary driver of mitochondrial dysfunction in aging; (4) Optimizes electron transport chain efficiency, reducing electron leak and ROS generation at complexes I and III; (5) Restores mitochondrial membrane potential and ATP production; (6) Prevents mitochondrial permeability transition pore opening, protecting against apoptosis; (7) Reduces age-related mitochondrial fragmentation and promotes healthy mitochondrial dynamics.
Molecular Formula
C32H49N5O5
Molecular Weight
639.8 g/mol
Sequence
D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyltyrosine)
Dosage Protocols
Dose Range
10mg – 40mg
Frequency
Once daily
Route
subcutaneous
Cycle Length
4-12 weeks (experimental)
Clinical trials used 4mg-40mg SC or IV daily. The 40mg SC dose was most commonly tested. Research peptide users typically use lower doses. No approved human dosing exists.
Source: Clinical trial protocols
Side Effects
| Effect | Severity |
|---|---|
| Injection site reaction | mild |
| Headache | mild |
| Nausea | mild |
| Fatigue | mild |
Pros & Cons
Scientifically elegant mechanism — directly targets the inner mitochondrial membrane and cardiolipin
Addresses the root cause of mitochondrial dysfunction rather than downstream symptoms
Extensive clinical trial program with human safety data from multiple Phase 2/3 studies
FDA Fast Track designation demonstrates regulatory recognition of the therapeutic potential
Broad potential applications: heart failure, aging, neurodegenerative disease, mitochondrial myopathies
Clinical trial results have been mixed — primary endpoints not always met despite promising biomarker data
Not yet approved by any regulatory agency despite years of clinical development
Expensive to synthesize due to non-natural amino acid (Dmt) requirement
Short half-life requiring daily injection; no oral formulation available
Research Studies
Legal Status
Investigational drug — FDA Fast Track designation for Barth syndrome. Not yet approved by FDA or other agencies. Phase 2/3 clinical trials completed for multiple indications with mixed results. Available from select research peptide suppliers.
Related Peptides
Semaglutide
An FDA-approved GLP-1 receptor agonist used for type 2 diabetes and chronic weight management, producing significant weight loss of 15-17% body weight in clinical trials.
BPC-157
A 15-amino acid synthetic peptide derived from human gastric juice that promotes healing of tendons, ligaments, muscles, gut lining, and other tissues through multiple regenerative pathways.
Tirzepatide
A first-in-class dual GIP/GLP-1 receptor agonist that produces up to 22.5% body weight loss, approved for type 2 diabetes and obesity management.
Ipamorelin
A highly selective growth hormone-releasing peptide (GHRP) that stimulates GH release with minimal impact on cortisol, prolactin, or appetite, making it the cleanest GHRP available.