Cell-Based hERG Channel Inhibition Assay in High-Throughput Format

Area of Science:

• Cardiovascular pharmacology
• Ion channel research
• Drug safety assessment

Background:

• The human ether-a-go-go-related gene (hERG) channel is crucial for cardiac action potential repolarization.
• Disruptions in hERG channel activity, due to genetic mutations or drug interactions, can lead to QT interval prolongation and long QT syndrome.
• Identifying compounds that affect hERG channel function is vital for drug safety and understanding cardiac electrophysiology.

Purpose of the Study:

• To describe a cell-based assay for identifying compounds that inhibit hERG channel activity.
• To present an optimized, high-throughput method for hERG channel inhibition screening.
• To establish a robust assay for assessing potential cardiac risks associated with chemical compounds.

Main Methods:

• Utilized the FluxOR™ thallium flux assay.
• Employed two cell lines with stable hERG expression: U2OS and HEK293.
• Adapted the assay for a 1536-well plate format for high-throughput screening.
• Developed a homogeneous and robust assay protocol.

Main Results:

• The described assay effectively identifies compounds that inhibit hERG channel activity.
• The assay is optimized for a 1536-well format, enabling efficient screening.
• The method is demonstrated to be homogeneous and robust for reliable results.

Conclusions:

• The optimized cell-based hERG channel inhibition assay is a valuable tool for drug discovery and safety.
• This high-throughput assay facilitates the identification of hERG channel blockers.
• The assay contributes to the assessment of potential cardiotoxicity and the risk of long QT syndrome.