The Safety Pharmacology Society is pleased to invite you to a webinar presentation on Thursday, January 30, 2020 at 11:00 EST, 16:00 UTC (GMT) / 17:00 CET.
Title: The Use of High-Throughput Multi Ion Channel Profiling and In Silico Modeling in Assessing Arrhythmia Risk: One Pharma’s Experience and Perspective
Presenter: Stephen Jenkinson, PhD, Director, In Vitro Safety Pharmacology, Pfizer, Inc.
Description: The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative has resulted in a shift in the ion channel profiling utilized to define proarrhythmic risk. Historically efforts focused mainly on the hERG channel and QTc prolongation, however, given the complex interplay between the various channel currents in generating and modulating the cardiac action potential, the focus has now shifted to a more comprehensive analysis that includes Nav1.5 and Cav1.2. The information gleaned has been used to generate a variety of in-silico models that aim to put these data sets into context with regards to predicting proarrhythmic risk.
Data analysis from various sites/profiling platforms has highlighted concerns around the reproducibility of patch clamp data between and within laboratories, especially with respect to automated systems. We present data encompassing a 12-month period from hERG, Nav1.5 and Cav1.2 channels using the Qube 384 high throughput system (Sophion, Denmark) and demonstrate high reproducibility for our standard compounds when using optimized protocols. In addition, we share proprietary screening data to highlight the ion channel profile of typical project compounds within Pfizer to highlight some key points with respect to profiling/risk assessments in a real-world environment in the context of CiPA. Additionally, we demonstrate the utility of an in house in-silico model that uses ion channel data and/or dofetilide binding data in combination with predicted clinical exposure to define a probability score for Torsades de Pointes risk.
Moderator: Simon Authier, DVM, MBA, PhD, DSP, Director Safety Pharmacology, Charles River Laboratories Montréal ULC
We look forward to your participation.
FREE for SPS Members
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