Erdemli, Gul, Mikhailov, Dmitri and Kim, Albert (2013) Indirect modulation of cardiac ion channels and implications for preclinical safety assessment. European Pharmaceutical Review.

Abstract

The preclinical assessment of a small molecule’s liability for QT interval prolongation is an essential part of the drug discovery process. Patch clamp assays for heterologously expressed recombinant cardiac ion channels are widely used in the pharmaceutical industry to evaluate potential drug-channel interactions. These assays are generally acute assessments and are not designed to detect indirect channel modulations that may result in QT prolongation. Despite the abundant literature demonstrating potential transcriptional, translational and post-translational mechanisms for indirect ion channel modulation, contribution of these mechanisms to drug-induced QT prolongation and/or arrhythmia propensity is not well understood. In this brief review we discuss some potential mechanisms through which indirect ion channel modulation can produce QT prolongation and strategies for their early detection and mitigation.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:16
Last Modified:	06 Jul 2016 23:45
URI:	https://oak.novartis.com/id/eprint/3240