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Mitochondrial-Targeted Peptide

SS-31 (Elamipretide)

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Overview

An investigational mitochondria-targeting tetrapeptide that binds the inner-membrane lipid cardiolipin; it has progressed through multiple human trials but is not approved, and results across indications have been mixed.

How it works

SS-31, known in clinical development as elamipretide, is a small synthetic peptide designed to concentrate inside mitochondria, the energy-producing compartments of cells. Its distinctive feature is that it accumulates at the inner mitochondrial membrane and associates with cardiolipin, a lipid that is essential for the machinery that generates cellular energy. The goal is to stabilize this machinery in tissues where mitochondria are stressed or failing.

By interacting with cardiolipin, the peptide is proposed to help preserve the structure of the electron transport chain, improve the efficiency of energy production, and reduce the leakage of damaging reactive oxygen species. Because almost every tissue depends on mitochondria, it has been explored across a broad range of conditions, including heart failure, certain inherited mitochondrial diseases, and age-related eye and muscle disorders.

It has been studied in numerous human clinical trials, which is why it is best described as investigational rather than merely preclinical. However, results have been inconsistent, with some studies failing to meet their primary goals, and it remains unapproved. Its real-world value is still being worked out, and it should not be regarded as a proven treatment.

Mechanism · Detailed Analysis
Molecular targetElamipretide is an aromatic-cationic tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that preferentially associates with cardiolipin in the inner mitochondrial membrane, rather than acting on a conventional cell-surface receptor.
Signaling & downstream effectsBy binding cardiolipin it is proposed to stabilize cristae architecture and electron-transport-chain supercomplexes, supporting more efficient ATP synthesis and reducing reactive oxygen species generation. These effects aim to improve bioenergetics in stressed mitochondria rather than to drive a specific signaling cascade.
PharmacokineticsIt is a peptide typically administered parenterally (e.g., subcutaneous or intravenous in trials) and is not reliably orally bioavailable. Its cell-penetrating, mitochondria-accumulating design is central to delivery; detailed human PK has been characterized within its clinical program.
CaveatsDespite an extensive trial program, efficacy results have been mixed and it is not approved. Benefits in any given condition remain unproven, and it should be regarded as investigational.
Published EvidenceLoading cited studies from PubMed…
Human Data ···

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Animal ···

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In Vitro ···

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Educational aggregation of public literature. Not medical advice and not a recommendation to use any compound. Many compounds here are not approved for human use. Consult a licensed clinician.