Use of high throughput ion channel profiling and statistical modeling to predict off-target arrhythmia risk - One pharma's experience and perspective

Autor: Eric D, Watt, Tiffany, Lee, Shuyun Lily, Feng, Peter, Kilfoil, David, Ackley, Christopher, Keefer, Todd, Wisialowski, Stephen, Jenkinson
Rok vydání: 2022
Předmět:
Zdroj: Journal of Pharmacological and Toxicological Methods. 118:107213
ISSN: 1056-8719
DOI: 10.1016/j.vascn.2022.107213
Popis: The use of high throughput patch clamp profiling to determine mixed ion channel-mediated arrhythmia risk was assessed using profiling data generated using proprietary internal and clinical reference compounds. We define the reproducibility of the platform and highlight inherent platform issues. The data generated was used to develop predictive models for cardiac arrhythmia risk, specifically Torsades de Pointes (TdP).A retrospective analysis was performed using profiling data generated over a 3-year period, including patch clamp data from hERG, CaAssay reproducibility was robust over the 3-year period examined. High throughput hERG patch ICThe data highlight the value of high throughput patch clamp data in the prediction of TdP risk, as well as some potential limitations with this approach.
Databáze: OpenAIRE