Drugs, hERG and sudden death

Area of Science:

• Pharmacology and Toxicology
• Drug Discovery and Development

Background:

• Early identification of drug-induced QT prolongation and Torsades de Pointes (TdP) liability is critical in drug development.
• The human Ether-à-go-go-Related Gene (hERG) assay is a mandatory component for Investigational New Drug (IND) applications.

Purpose of the Study:

• To address the limitations of the current gold standard hERG assay for early-stage drug discovery.
• To explore the need for high-throughput screening methods to assess potential hERG channel interactions early in the drug development pipeline.

Main Methods:

• The study discusses the limitations of the standard hERG assay, including its labor-intensive nature and low throughput.
• It highlights the use of various indirect high-throughput screening (HTS) assays as alternatives for early-stage assessment.

Main Results:

• The hERG assay, while essential for IND applications, is not suitable for initial high-throughput screening due to its low throughput.
• Indirect HTS methods have been employed to overcome these throughput limitations.

Conclusions:

• There is a clear need for efficient, high-throughput screening methods to evaluate early drug candidates for hERG liability.
• Implementing such assays early can streamline the drug discovery and development process, reducing costs and time.