Evolution of strategies to improve preclinical cardiac safety testing

G Gintant, PT Sager, N Stockbridge - Nature reviews Drug discovery, 2016 - nature.com
The early and efficient assessment of cardiac safety liabilities is essential to confidently
advance novel drug candidates. This article discusses evolving mechanistically based …

[HTML][HTML] The comprehensive in vitro proarrhythmia assay (CiPA) initiative—update on progress

T Colatsky, B Fermini, G Gintant, JB Pierson… - … of pharmacological and …, 2016 - Elsevier
The implementation of the ICH S7B and E14 guidelines has been successful in preventing
the introduction of potentially torsadogenic drugs to the market, but it has also unduly …

Comprehensive in vitro Proarrhythmia Assay, a novel in vitro/in silico paradigm to detect ventricular proarrhythmic liability: a visionary 21st century initiative

I Cavero, H Holzgrefe - Expert opinion on drug safety, 2014 - Taylor & Francis
Introduction: The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a novel safety
screening proposal intended to replace the 2005 regulatory strategy recommended by the …

An automated fitting procedure and software for dose-response curves with multiphasic features

GY Di Veroli, C Fornari, I Goldlust, G Mills, SB Koh… - Scientific reports, 2015 - nature.com
In cancer pharmacology (and many other areas), most dose-response curves are
satisfactorily described by a classical Hill equation (ie 4 parameters logistical). Nevertheless …

Optimization of an In silico Cardiac Cell Model for Proarrhythmia Risk Assessment

S Dutta, KC Chang, KA Beattie, J Sheng… - Frontiers in …, 2017 - frontiersin.org
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many
drugs from the market and is therefore of major concern to global regulatory agencies and …

Improving the in silico assessment of proarrhythmia risk by combining hERG (human ether-à-go-go-related gene) channel–drug binding kinetics and multichannel …

Z Li, S Dutta, J Sheng, PN Tran, W Wu… - Circulation …, 2017 - Am Heart Assoc
Background—The current proarrhythmia safety testing paradigm, although highly efficient in
preventing new torsadogenic drugs from entering the market, has important limitations that …

Systems toxicology: real world applications and opportunities

T Hartung, RE FitzGerald, P Jennings… - Chemical research in …, 2017 - ACS Publications
Systems Toxicology aims to change the basis of how adverse biological effects of
xenobiotics are characterized from empirical end points to describing modes of action as …

Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells

J Kramer, HM Himmel, A Lindqvist, S Stoelzle-Feix… - Scientific reports, 2020 - nature.com
Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic
effects of drugs on human cardiac currents in heterologous expression systems. Differences …

Natural products modulating the hERG channel: heartaches and hope

JM Kratz, U Grienke, O Scheel, SA Mann… - Natural product …, 2017 - pubs.rsc.org
Covering: 1996–December 2016 The human Ether-à-go-go Related Gene (hERG) channel
is a voltage-gated potassium channel playing an essential role in the normal electrical …

In Silico Classifiers for the Assessment of Drug Proarrhythmicity

J Llopis-Lorente, J Gomis-Tena, J Cano… - Journal of Chemical …, 2020 - ACS Publications
Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia
responsible for the withdrawal of many drugs from the market. Although currently used TdP …