Evolution of strategies to improve preclinical cardiac safety testing

Nat Rev Drug Discov. 2016 Jul;15(7):457-71. doi: 10.1038/nrd.2015.34. Epub 2016 Feb 19.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Cardiotoxicity / diagnosis*
  • Cardiotoxicity / metabolism
  • Cells, Cultured
  • Drug Evaluation, Preclinical*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / physiology
  • Ion Channels / antagonists & inhibitors*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Risk Assessment
  • Safety


  • Calcium Channel Blockers
  • Ion Channels