HTS techniques to investigate the potential effects of compounds on cardiac ion channels at early-stages of drug discovery.
Within the past few years, the high-throughput screening (HTS) of compounds targeting cardiac ion channels has been primarily focused on the testing of the HERG channel, which is involved in the termination of cardiac action potential. Interaction of drugs with this channel may induce QT interval prolongation and cardiac arrhythmia. These undesirable side effects have forced several pharmaceutical companies to terminate drug discovery and development projects. The screening of compounds for HERG-mediated activity early in the drug development process may thus help reduce the number of compounds that are withdrawn from late preclinical or early clinical trials due to cardiovascular side effects. However, early screening implies the ability to test large numbers of compounds. Therefore, tests have to be performed rapidly, combining high-throughput and low costs, and allow the use of small amounts of compounds. In this review, the HTS systems currently available to investigate the potential effects of compounds on the activity of the cardiac HERG ion channel will be described and compared.
Netzer
Rainer
R
Evotec OAI Schnackenburgallee 114 22525 Hamburg, Germany. rainer.netzer@evotecoai.com
Bischoff
Ulrike
U
Ebneth
Andreas
A
D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008133:Long QT Syndrome / Q000188:drug therapy / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D012413:Rubidium
D005456:Fluorescent Dyes; D007473:Ion Channels; D012413:Rubidium