title: Cardiac safety pharmacology: from human ether-a-gogo related gene channel block towards induced pluripotent stem cell based disease models.
abstract: BACKGROUND
  The field of cardiac safety pharmacology has been experiencing exciting changes over the recent years. Drug induced arrhythmia of the torsade des pointes types has been the reason for the denial of approval of novel drug candidates. The aim of cardiac safety pharmacology is to detect undesirable pharmacodynamic drug effects within and above the therapeutic range. A special focus is on the identification of potential arrhythmogenic effects within the drug discovery chain.
  
  
  METHODS
  Here, the authors discuss the relevance of induced pluripotent stem (iPS) cell derived cardiomyocytes for safety pharmacology. The technology of obtaining functional cardiomyocytes from somatic cells of healthy donors and patients with inherited diseases is the basis for diverse disease models in multi-level safety pharmacology screening. The reader will gain an overview of stem cell based technologies in cardiac safety pharmacology in cardiac and disease modeling by iPS cell derived cardiomyocytes from patients with an inherited cardiac syndrome.
  
  
  CONCLUSIONS
  iPS cell derived cardiomyocytes - especially from patients with increased risk of cardiac arrhythmia - are on the verge of offering new options for drug testing. More reliable assays can be expected to predict the arrhythmogenic risk of drug candidates in humans. However, this technology is still new and extensive validation studies are due.
authors: Multi Channel Systems, Reutlingen, Germany. udo.kraushaar@nmi.de
authors: Udo
authors: U
authors: Kraushaar
authors: Thomas
authors: T
authors: Meyer
authors: Dietmar
authors: D
authors: Hess
authors: Lior
authors: L
authors: Gepstein
authors: Christine L
authors: CL
authors: Mummery
authors: Stefan R
authors: SR
authors: Braam
authors: Elke
authors: E
authors: Guenther
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001681:Biological Assay; D002478:Cells, Cultured; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels