SS-31
Elamipretide
Longevity & Cellular Aging
CAS
736992-21-5
Molecular Weight
640
Da
Observational
A mitochondria-targeting tetrapeptide developed by Hazel Szeto at Weill Cornell that selectively concentrates in the inner mitochondrial membrane and stabilizes cardiolipin, a phospholipid essential for electron transport chain function. One of the few compounds in the Longevity category to reach Phase III clinical trials. The pivotal Phase 3 (MMPOWER-3) failed its primary endpoints in primary mitochondrial myopathy; Barth syndrome (TAZPOWER) showed meaningful 48-week benefit. Strong foundational science, mixed human translation.
Injectable
Intranasal Suitable
No
Research Compound
Community Signal
SS-31 discussion in longevity and biohacking communities is growing but remains niche, partly because subcutaneous injection is a practical barrier, partly because the MMPOWER-3 failure tempered enthusiasm among more evidence-following community members. The most engaged discussion clusters in mitochondrial disease patient communities (Barth syndrome, MELAS) where TAZPOWER results are treated with genuine cautious optimism. In general longevity circles, SS-31 is frequently discussed alongside MOTS-c as an example of a "mitochondria-targeted" approach distinct from NAD+ supplementation, intellectually compelling, but with a higher translation-to-clinic risk profile than it initially appeared. Injection site reactions are frequently mentioned in self-experiment accounts as the primary tolerability concern.
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What It Is
SS-31 is a synthetic tetrapeptide belonging to the Szeto-Schiller peptide family, designed with specific structural features that allow it to penetrate cell membranes and selectively accumulate in mitochondria at concentrations 1,000 to 5,000 times higher than in the cytoplasm. This selectivity is achieved through an alternating aromatic-cationic amino acid pattern that facilitates interaction with the inner mitochondrial membrane. Once there, SS-31 binds cardiolipin, a phospholipid unique to the inner mitochondrial membrane , stabilizing mitochondrial cristae architecture and optimizing the organization and function of the electron transport chain. The compound represents a distinct mechanistic approach from NAD+ precursors (NMN) or mitophagy enhancers: rather than increasing mitochondrial production, it improves the efficiency and structural integrity of existing mitochondria.
Mechanism of Action
SS-31 binds to cardiolipin in the inner mitochondrial membrane, where cardiolipin serves as an essential structural scaffold for the respiratory complex supercomplexes (Complexes I, III, and IV) that perform oxidative phosphorylation. Mitochondrial dysfunction, whether from aging, disease, or ischemic injury, involves cardiolipin peroxidation and subsequent disruption of cristae structure, which impairs electron transport efficiency and increases reactive oxygen species (ROS) leakage. By binding peroxidized cardiolipin, SS-31 stabilizes cristae morphology, reduces ROS production, restores electron transport efficiency, and enhances ATP synthesis. It also inhibits cytochrome c peroxidase activity, preventing further cardiolipin oxidation. In preclinical models, this translates to reduced ischemia-reperfusion injury, improved cardiac function, protection against muscle atrophy, and reversal of age-related mitochondrial dysfunction. In human trials, the translation has been more variable.
Use Cases
Clinical trial indications: Primary mitochondrial myopathy (MMPOWER-2/3), Barth syndrome (TAZPOWER), heart failure with reduced ejection fraction (PROGRESS-HF), age-related macular degeneration (ReCLAIM)
Community/longevity use: Mitochondrial function optimization, age-related energy decline, exercise recovery, neuroprotection
Active research: Friedreich's ataxia, ischemic kidney disease, dry AMD
Known Risks
SS-31 has demonstrated a favorable safety profile across clinical trials, the most common adverse event is injection site reaction (redness, swelling at subcutaneous injection site), which occurred in a meaningful proportion of participants but was generally mild. No serious adverse events were attributed to the compound in MMPOWER-3, TAZPOWER, or PROGRESS-HF. Long-term safety beyond 48 weeks has limited data. Oral bioavailability is negligible due to peptide degradation in the GI tract, subcutaneous or intravenous administration is required for any meaningful systemic effect. This is a significant practical consideration for community use, as the compound cannot be effectively taken orally.
Available Forms
SS-31 has no FDA-approved commercial formulation. In clinical trials it has been administered subcutaneously (40 mg/day in MMPOWER-3 and TAZPOWER) or intravenously (PROGRESS-HF). Oral administration is ineffective due to rapid peptide degradation, this is a firm pharmacokinetic constraint, not a dosing preference. SS-31 is available as a research chemical from peptide synthesis suppliers, typically as a lyophilized powder requiring reconstitution for subcutaneous injection. Compounding pharmacies with peptide capabilities can produce it, though it sits in a regulatory gray zone as an investigational compound with no approved indication. Stealth BioTherapeutics, the company that developed it clinically, filed for bankruptcy in 2022; IP has since been acquired by other parties and investigator-initiated trials continue.
Regulatory Status
SS-31 (elamipretide) has no FDA-approved indication in any formulation. It was studied under multiple Investigational New Drug (IND) applications by Stealth BioTherapeutics across several disease areas. The company's bankruptcy in 2022 following the MMPOWER-3 failure terminated its commercial development pipeline, though investigator-initiated academic trials continue under existing INDs. In the US, it is not commercially available and is not eligible for compounding under standard 503A pharmacy regulations as a compound that is essentially a copy of a previously approved drug, however, because it was never approved, it occupies a gray zone that some compounders navigate. Internationally, no major regulatory agency has approved it in any indication.
Sources
https://pubmed.ncbi.nlm.nih.gov/29500292/
https://pubmed.ncbi.nlm.nih.gov/33077895/
https://pubmed.ncbi.nlm.nih.gov/24117165/
Similar Compounds
MOTS-c, NMN, Humanin
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