SS-31 (elamipretide) — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for SS-31 (elamipretide), with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Cardiolipin (inner mitochondrial membrane) | Direct binding | Not a receptor interaction; the peptide associates with the lipid and stabilises cristae architecture and electron-transport-chain supercomplexes |
§2.2Mechanism of action
Elamipretide binds cardiolipin in the inner mitochondrial membrane, stabilising cristae curvature and the assembly of electron-transport-chain supercomplexes, and reducing cytochrome-c peroxidase activity. The result in preclinical models is improved oxidative phosphorylation efficiency and reduced reactive oxygen species generation. The mechanism is unusual among the compounds in this series in being a specific, well-characterised lipid interaction rather than a receptor hypothesis.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- ≈1–2 h in plasma; tissue mitochondrial accumulation persists longer
- Time to maximum concentration
- ≈1 h after subcutaneous administration
- Volume of distribution
- large apparent volume reflecting mitochondrial partitioning
- Plasma protein binding
- moderate
- Clearance
- not published
- Bioavailability
- well absorbed subcutaneously
Proteolysis and renal excretion. Plasma pharmacokinetics understate the pharmacodynamic duration because the site of action is an intracellular membrane compartment.
§2.4Interactions
- Not characterised as clinically significant
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology 2014;171(8):2029–2050. doi:10.1111/bph.12461 · PMID 24117165
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.