Evolution of strategies to improve preclinical cardiac safety testing
This article discusses evolving preclinical strategies for detecting drug-induced cardiotoxicity using human ion-channel assays, human-based in silico reconstructions and human stem cell-derived cardiomyocytes. Such strategies have the potential to improve the early detection of genuine cardiotoxici...
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Veröffentlicht in: | Nature reviews. Drug discovery 2016-07, Vol.15 (7), p.457-471 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | This article discusses evolving preclinical strategies for detecting drug-induced cardiotoxicity using human ion-channel assays, human-based
in silico
reconstructions and human stem cell-derived cardiomyocytes. Such strategies have the potential to improve the early detection of genuine cardiotoxicity risks, reducing the likelihood of mistakenly discarding viable drug candidates and speeding worthy drugs into clinical trials.
The early and efficient assessment of cardiac safety liabilities is essential to confidently advance novel drug candidates. This article discusses evolving mechanistically based preclinical strategies for detecting drug-induced electrophysiological and structural cardiotoxicity using
in vitro
human ion channel assays, human-based
in silico
reconstructions and human stem cell-derived cardiomyocytes. These strategies represent a paradigm shift from current approaches, which rely on simplistic
in vitro
assays that measure blockade of the K
v
11.1 current (also known as the hERG current or I
Kr
) and on the use of non-human cells or tissues. These new strategies have the potential to improve sensitivity and specificity in the early detection of genuine cardiotoxicity risks, thereby reducing the likelihood of mistakenly discarding viable drug candidates and speeding the progression of worthy drugs into clinical trials. |
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ISSN: | 1474-1776 1474-1784 |
DOI: | 10.1038/nrd.2015.34 |