Evaluation of an in silico cardiac safety assay: using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge.

ABSTRACT:

Introduction

Drugs that prolong the QT interval on the electrocardiogram present a major safety concern for pharmaceutical companies and regulatory agencies. Despite a range of assays performed to assess compound effects on the QT interval, QT prolongation remains a major cause of attrition during compound development. In silico assays could alleviate such problems. In this study we evaluated an in silico method of predicting the results of a rabbit left-ventricular wedge assay.

Methods

Concentration-effect data were acquired from either: the high-throughput IonWorks/FLIPR; the medium-throughput PatchXpress ion channel assays; or QSAR, a statistical IC50 value prediction model, for hERG, fast sodium, L-type calcium and KCNQ1/minK channels. Drug block of channels was incorpor

SUBMITTER: Beattie KA 

PROVIDER: S-EPMC4142193 | biostudies-literature | 2013 Jul-Aug

REPOSITORIES: biostudies-literature