Recursos Técnicos - Posters Científicos

Analysis of a New High Throughput Screening Detection Technology for Rapid hERG Safety Testing using a Fluorescence Polarization Assay

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January 14, 2013


Authors: Wendy Goodrich, Gary Prescott and Andreas Rieger, BioTek Instruments, Inc., Winooski, Vermont; Mark Koeppe, Invitrogen Life Technologies, Madison, Wisconsin

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Introduction

 

The vast majority of drugs associated with acquired QT prolongation are known to interact with hERG. Due to the awareness of the potential danger of such QT drugs, regulatory authorities issued requirements for the establishment of cardiac safety testing during preclinical drug development. Traditionally, lead compounds in late stage preclinical studies were tested for hERG binding using electrophysiology. These laborious methods required significant skill in the end-user to perform a successful assay. Furthermore, many researchers wish to test lead compounds for safety earlier in the process of drug development. This requires a higher throughput type of assay. Here we describe a new HTS detection platform suitable for hERG screening via fluorescence polarization based assay. Using assay controls and a panel of multiple hERG inhibitors, analysis of pharmacology endpoints for instrument validation include Z’, assay window, precision and plate read times. Additionally, FP-based IC50 data is generated and compared to electrophysiology and radiometric data.

 


 

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