Topsalysin pore complex (PSA-activated Topsalysin pore)

The Topsalysin pore complex is a drug-induced cytolytic structure formed on the surface of prostate cells. It is the functional product of Topsalysin (PRX302), a genetically modified aerolysin pro-toxin engineered to be selectively activated by the serine protease prostate-specific antigen (PSA) (Denmeade et al., 2012). Upon cleavage by PSA, the pro-toxin's inhibitory C-terminal peptide is removed, allowing the resulting active monomers to oligomerize into a stable heptameric pore that inserts into the plasma membrane (Sophiris Bio, 2020). This pore creates a non-selective channel approximately 1-2 nanometers in diameter, disrupting the cell's osmotic balance and leading to rapid influx of water, cell swelling, and necrotic cell death known as cytolysis (Williams et al., 2007). This targeted approach allows for the focal destruction of prostate tissue in conditions such as benign prostatic hyperplasia (BPH) and localized prostate cancer while minimizing damage to adjacent tissues that lack high concentrations of active PSA (ClinicalTrials.gov, NCT02432209). The specificity of the complex is maintained by the requirement for active PSA, which is found in high concentrations almost exclusively within the prostate microenvironment.

Other names

Prostate-specific antigen-activated Topsalysin pore complex on prostate cell membranesPRX302 porePSA-activated aerolysin poreTopsalysin heptameric porePSA-activated pore-forming toxin

Topsalysin is a pro-toxin that is enzymatically activated by prostate-specific antigen (PSA) within the prostate; the active monomers then oligomerize to form a heptameric pore complex that inserts into the prostate cell membrane, causing rapid osmotic lysis and cell death.