Referenced in: none

Automatically associated channels: Kv11.1

Title: In vitro profiling against ion channels beyond hERG as an early indicator of cardiac risk.

Authors: Mao Xiang Chen, Ray M Helliwell, Jeff J Clare

Journal, date & volume: Curr. Opin. Mol. Ther., 2009 Jun , 11, 269-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19479660

Abstract
Acquired long QT syndrome is a major cause of drug withdrawals and the failure of compounds during development. Traditionally, in vitro cardiac liability screens have been low throughput and expensive, and have used primary animal cells or tissues that are not necessarily predictive of the human heart. Recent advances in ion channel assay technologies, particularly automated patch clamp, have enabled the early liability screening of individual ion channels at medium-to-high throughput and with acceptable fidelity. The primary aim of this first-tier screening is to aid prioritization of early-stage compounds for progression along the screening cascade. Potential liabilities can be flagged to enable follow-up studies to be initiated if and when compounds approach the costlier stages of development. To date, cardiac safety screening has been focused on hERG channel. This article examines the rationale for the early screening of cardiac channels beyond hERG as part of an integrated strategy for in vitro evaluation of cardiac risk, and reviews recent developments in the relevant technologies.