An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.
Keyword
arrhythmiascardiotoxicity
computer simulation
induced pluripotent stem cells
ion channels
preclinical drug evaluation
Journal title
British journal of pharmacologyDate Published
2022-07-24Publication Volume
179Publication Issue
20Publication Begin page
4829Publication End page
4843Metadata
Show full item recordAbstract
Significant AP prolongation (a pro-arrhythmia marker) was seen in response to quinidine and quinine. The VC protocol identified block of IKr (a source of arrhythmias) by all strong IKr blockers, including cisapride, quinidine and quinine. The protocol also detected block of ICaL by verapamil and Ito by quinidine. Further demonstrating the power of the approach, the VC data uncovered a previously unidentified If block by quinine, which was confirmed with experiments using a HEK-293 expression system and automated patch-clamp.DOI
10.1111/bph.15915Scopus Count
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Except where otherwise noted, this item's license is described as © 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.