Back to Search
Start Over
Evolution of strategies to improve preclinical cardiac safety testing.
- Source :
-
Nature reviews. Drug discovery [Nat Rev Drug Discov] 2016 Jul; Vol. 15 (7), pp. 457-71. Date of Electronic Publication: 2016 Feb 19. - Publication Year :
- 2016
-
Abstract
- 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 Kv11.1 current (also known as the hERG current or IKr) 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.
- Subjects :
- Animals
Cardiotoxicity metabolism
Cells, Cultured
Humans
Induced Pluripotent Stem Cells drug effects
Induced Pluripotent Stem Cells physiology
Myocytes, Cardiac drug effects
Myocytes, Cardiac physiology
Risk Assessment
Safety
Calcium Channel Blockers pharmacology
Cardiotoxicity diagnosis
Drug Evaluation, Preclinical
Induced Pluripotent Stem Cells cytology
Ion Channels antagonists & inhibitors
Myocytes, Cardiac cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1474-1784
- Volume :
- 15
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Nature reviews. Drug discovery
- Publication Type :
- Review
- Accession number :
- 26893184
- Full Text :
- https://doi.org/10.1038/nrd.2015.34