Kinetics of drug binding to hERG at room temperature

This collection contains raw data files (pClamp format) relating to the measurement of the kinetics of drug binding to hERG channels at ambient temperatures. Data was acquired on behalf of the Ion Channel Working Group of CiPA, funded by the Safety Pharmacology Society.\n\nA description of methods and implementation is published in the manuscript: Measuring Potency and Kinetics of hERG block for CiPA in Journal of Pharmacological and Toxicological methods.\n\nAbstract:\nThe Comprehensive in vitro Proarrhythmic assay (CiPA) aims to update current cardiac safety testing to better evaluate arrhythmic risk. A central theme of CiPA is the use of in silico approaches to risk prediction incorporating models of drug binding to hERG. To parameterize these models, accurate in vitro measurement of potency and kinetics of block is required. The Ion Channel Working Group was tasked with: i) selecting a protocol that could measure kinetics of block and was easily implementable on automated platforms for future rollout in industry and ii) acquiring a reference dataset using the standardized protocol. Potency, kinetics and trapping characteristics of hERG block for the CiPA training panel of twelve drugs were measured. Timecourse of block and trapping characteristics could be reliably measured if the time constant for onset of block was between ~500 ms and ~15 sec. Seven drugs, however had time courses of block faster than this cut-off. The dataset from this study is being used by the In Silico Working Group to develop models of drug binding for risk prediction and is being made here freely available as a ‘gold standard’ ambient temperature dataset to evaluate variability across high throughput platforms.