AI Article Synopsis
- Aspidasept (Pep19-2.5) and its derivative, Pep19-4LF (Aspidasept II), are synthetic polypeptides designed to combat moderate to severe bacterial infections and associated systemic inflammation, like sepsis.
- The study examined the toxic behavior of these peptides in various cell models and electrophysiological experiments, particularly focusing on their effects on the hERG channel, which is critical for heart health.
- Findings from mouse and rat models have helped establish a therapeutic window for the safe use of Aspidasept, paving the way for potential clinical applications.
Article Abstract
Aspidasept (Pep19-2.5) and its derivative Pep19-4LF ("Aspidasept II") are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782211 | PMC |
| http://dx.doi.org/10.3390/microorganisms10122412 | DOI Listing |
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