SS-31

Szeto-Schiller Peptide 31 — Mitochondria-Targeting Antioxidant

Half-life: ~2–4 hours (SC)

ElamipretideMTP-131Bendavia

Research Profile

Research Depth

Potency

Half-Life Score

Selectivity

Stability

Relative research assessments — educational reference only.

Target Receptors

Cardiolipin (direct binding)Inner mitochondrial membrane

Critical Research Warning

For educational reference only. Phase 3 trial for Barth syndrome missed primary endpoint. Efficacy in broader populations unconfirmed.

PeptidePlaza Entry #019

"A cell-permeable tetrapeptide that selectively concentrates in the inner mitochondrial membrane by binding cardiolipin. Protects mitochondrial cristae structure and reduces oxidative stress without scavenging ROS directly."

Full Description

SS-31 (D-Arg-Dmt-Lys-Phe-NH₂) is a synthetic aromatic-cationic tetrapeptide from the Szeto-Schiller series designed to target the inner mitochondrial membrane. It concentrates 1000-fold in mitochondria via electrostatic and hydrophobic interactions with cardiolipin — a phospholipid unique to the inner mitochondrial membrane essential for electron transport chain efficiency. By stabilizing cardiolipin, SS-31 preserves cristae structure, reduces cytochrome c release, and dramatically reduces mitochondrial ROS without directly scavenging free radicals. It has demonstrated efficacy in models of heart failure, ischemia-reperfusion, renal disease, and age-related muscle decline.

Mechanism of Action

Binds cardiolipin on the inner mitochondrial membrane. Stabilizes cristae structure and preserves Complex I/III/IV electron transport efficiency. Reduces mitochondrial ROS via cardiolipin protection rather than direct scavenging. Prevents cytochrome c release and apoptosis.

Reported Benefits

• Mitochondria-specific cardiolipin stabilization
• Reduced mitochondrial ROS at source (not scavenging)
• Improved cardiac function and exercise capacity in Phase 2

Potential Side Effects

• Injection site pain and erythema
• Transient blood pressure decrease
• Nausea reported in some trial participants

Frequently Asked Questions

How does SS-31 differ from other antioxidants?▼

Unlike conventional antioxidants (vitamin C, NAC) that float freely through cells and can paradoxically worsen oxidative stress, SS-31 concentrates 1000-fold specifically inside mitochondria and stabilizes cardiolipin — preventing ROS production at its source rather than scavenging ROS after they form.

What clinical trials has SS-31 been in?▼

SS-31 (Elamipretide) has completed Phase 2 trials for heart failure, Barth syndrome, and mitochondrial myopathy. It showed promising signals in cardiac function and exercise capacity but the Phase 3 Barth syndrome trial missed its primary endpoint in 2023.

For Research Reference Only

Not medical advice. Peptides may be regulated or restricted in your jurisdiction.

References

1.Mitochondrial-targeted SS-31 peptide attenuates radiation-induced cardiomyocyte senescence. PubMed (2026). Xie L, et al.. pubmed.ncbi.nlm.nih.gov/42456009/ ↑
2.Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence. PubMed (2026). Fan J, et al.. pubmed.ncbi.nlm.nih.gov/42450582/ ↑
3.Elamipretide (SS-31) and Nicotinamide Mononucleotide (NMN) Combination Therapy Targets TREM2 to Mitigate Post-ischemic Brain Injury in Mice. PubMed (2026). Yang Q, et al.. pubmed.ncbi.nlm.nih.gov/42443448/ ↑
4.Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model. PubMed (2026). Vahle B, et al.. pubmed.ncbi.nlm.nih.gov/42290373/ ↑