A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm
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Bradley J. Ridder, Derek J. Leishman, Matthew Bridgland-Taylor, Mohammadreza Samieegohar, Xiaomei Han, Wendy W. Wu, Aaron Randolph, Phu Tran, Jiansong Sheng, Timm Danker, Anders Lindqvist, Daniel Konrad, Simon Hebeisen, Liudmila Polonchuk, Evgenia Gissinger, Muthukrishnan Renganathan, Bryan Koci, Haiyang Wei, Jingsong Fan, Paul Levesque, Jae Kwagh, John Imredy, Jin Zhai, Marc Rogers, Edward Humphries, Robert Kirby, Sonja Stoelzle-Feix, Nina Brinkwirth, Maria Giustina Rotordam, Nadine Becker, Søren Friis, Markus Rapedius, Tom A. Goetze, Tim Strassmaier, George Okeyo, James Kramer, Yuri Kuryshev, Caiyun Wu, Herbert Himmel, Gary R. Mirams, David G. Strauss, Remi Bardenet, Zhihua Li
hERG block potency is widely used to calculate a drug’s safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed.