SS-31 10mg
A mitochondria-targeted aromatic-cationic tetrapeptide that selectively concentrates in the inner mitochondrial membrane and stabilizes cardiolipin—supporting electron transport chain function, reducing reactive oxygen species generation, and protecting mitochondrial cristae architecture in models of ischemia, heart failure, and aging.
The Science
What is SS-31 (Elamipretide)?
SS-31, developed under the clinical name elamipretide (MTP-131), is a synthetic aromatic-cationic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂ (where Dmt is 2',6'-dimethyltyrosine). It belongs to the Szeto-Schiller (SS) peptide family and is uniquely engineered to selectively concentrate in the inner mitochondrial membrane (IMM) at concentrations dramatically higher than in the cytoplasm—driven by its alternating cationic and aromatic amino acid motif interacting with the anionic phospholipid cardiolipin.
The defining biochemical interaction of SS-31 is its high-affinity binding to cardiolipin, a phospholipid found almost exclusively in the IMM where it is essential for organizing the electron transport chain (ETC) supercomplexes, maintaining cristae architecture, and retaining cytochrome c. Cardiolipin is highly susceptible to oxidative damage; peroxidized cardiolipin loses cytochrome c, disrupts ETC organization, and triggers apoptosis. SS-31 prevents cardiolipin peroxidation and restores its structural and functional roles.
Elamipretide has been evaluated in multiple Phase 2 and Phase 3 clinical trials for heart failure with reduced ejection fraction (HFrEF), primary mitochondrial myopathy (MMPOWER studies), and Barth syndrome—a rare cardiolipin-metabolism disorder. It has received FDA Orphan Drug Designation and represents the most clinically advanced mitochondria-targeted peptide in human research.
Laboratory Observations
Research-Observed Areas of Interest
Heart Failure and Cardiac Ischemia-Reperfusion
SS-31 has demonstrated improvements in cardiac energy metabolism, left ventricular function, and exercise capacity in heart failure models and early human trials. The Phase 2 EMBRACE-HF trial showed significant reduction in pulmonary capillary wedge pressure following short-term infusion in HFrEF research subjects.
Primary Mitochondrial Myopathy
The MMPOWER-3 Phase 3 trial evaluated elamipretide in primary mitochondrial myopathy. While the primary endpoint (distance walked in 6 minutes) did not reach statistical significance versus placebo, research subject-reported outcomes on fatigue and function showed consistent improvement, supporting ongoing research.
Barth Syndrome
Barth syndrome is caused by mutations in tafazzin, an enzyme required for cardiolipin remodeling. SS-31's direct cardiolipin-stabilizing mechanism provides strong mechanistic rationale; case series and early trials have shown improvements in cardiac and skeletal muscle function in Barth research subjects.
Renal Ischemia-Reperfusion Protection
Animal research demonstrates SS-31 substantially reduces renal tubular injury biomarkers and functional impairment in ischemia-reperfusion models, with proposed clinical application in kidney transplantation and cardiac surgery contexts.
Age-Related Mitochondrial Decline
Research suggests SS-31 can partially restore mitochondrial morphology and bioenergetic capacity in aged animal models, improving exercise capacity and muscle function—positioning it as a research tool for studying mitochondrial contributions to aging phenotypes.
Mechanism of Action
How SS-31 Works
Cardiolipin Binding and Peroxidation Prevention
SS-31 binds directly to cardiolipin in the IMM, stabilizing its conformation and protecting its acyl chains from lipid peroxidation by reactive oxygen species. By preserving cardiolipin integrity, SS-31 maintains the structural scaffolding necessary for ETC supercomplex assembly and cytochrome c retention—restoring the physical architecture required for efficient oxidative phosphorylation.
ETC Efficiency Improvement and ROS Reduction
By stabilizing ETC supercomplex organization, SS-31 improves electron flow through Complexes I–IV, reduces electron leak to molecular oxygen (the primary source of superoxide), and thereby decreases mitochondrial ROS production. This dual effect—more ATP per substrate oxidized and less oxidative damage generated—underlies SS-31's cytoprotective profile in ischemia-reperfusion and heart failure models.
Cristae Morphology Preservation
Mitochondrial cristae fragmentation is a hallmark of mitochondrial dysfunction and cell stress. SS-31 has been shown to mitigate cristae network fragmentation following cardiac ischemia-reperfusion (Communications Biology, 2020), preserving the expansive surface area needed for ATP synthesis and reducing cytochrome c release that would otherwise trigger apoptosis.
FAQ
Frequently Asked Questions
What makes SS-31 different from other antioxidants like CoQ10?+
Conventional antioxidants like CoQ10 scavenge ROS after they are produced. SS-31 acts upstream—by stabilizing cardiolipin and ETC supercomplexes, it prevents the electron leak that generates ROS in the first place, while also restoring efficient ATP production. This addresses the root bioenergetic problem rather than only the oxidative downstream consequence.
Why is cardiolipin so important?+
Cardiolipin is a unique phospholipid found almost exclusively in the inner mitochondrial membrane. It acts as structural scaffolding for ETC supercomplexes (respirasomes), tethers cytochrome c to facilitate electron transfer, and helps maintain cristae morphology. Its peroxidation by ROS unravels this architecture, disrupting energy production and triggering apoptosis—making it a central node in mitochondrial pathology.
Has elamipretide shown benefit in human clinical trials?+
Clinical results have been mixed. Phase 2 data in heart failure showed significant improvements in hemodynamic parameters. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its primary endpoint but showed research subject-reported functional benefits. Research is ongoing and the compound retains FDA Orphan Drug Designation.
Research-Only Notice
SS-31 10mg is categorized by the FDA as for research-purposes-only. It is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease. The information above summarizes effects observed in laboratory studies to date and is provided strictly for scientific and educational reference.