ReviewBritish journal of pharmacology2008
Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.
Review in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Model-based evaluation of drug-induced QTc prolongation for compounds in early development.British journal of clinical pharmacology · 2015Trial
- Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy.Science advances · 2025Article
- Phα1β interaction with the Kv11.1 potassium channel in HEK293 cells transfected with the human ERG channel.The journal of venomous animals and toxins including tropical diseases · 2025Article
- Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.Frontiers in cardiovascular medicine · 2024Review
- Characterization and Validation of a Human 3D Cardiac Microtissue for the Assessment of Changes in Cardiac Pathology.Scientific reports · 2018Article
- Drug-Induced Arrhythmias, Precision Medicine, and Small Data.Circulation. Arrhythmia and electrophysiology · 2017Article
- Administration of Non-Torsadogenic human Ether-à-go-go-Related Gene Inhibitors Is Associated with Better Survival for High hERG-Expressing Glioblastoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Inter-individual variability and modeling of electrical activity: a possible new approach to explore cardiac safety?Scientific reports · 2016Article
- Early Drug Discovery Prediction of Proarrhythmia Potential and Its Covariates.The AAPS journal · 2015Article
- Mycobacterium tuberculosis gyrase inhibitors as a new class of antitubercular drugs.Antimicrobial agents and chemotherapy · 2015Article
- Video image-based analysis of single human induced pluripotent stem cell derived cardiomyocyte beating dynamics using digital image correlation.Biomedical engineering online · 2014Article
- Not-in-trial simulation I: Bridging cardiovascular risk from clinical trials to real-life conditions.British journal of clinical pharmacology · 2013Article
- A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards.Journal of cardiovascular translational research · 2013Review
- Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing.British journal of pharmacology · 2012Review
- Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture.Disease models & mechanisms · 2012Article
- On the relationship between block of the cardiac Na⁺ channel and drug-induced prolongation of the QRS complex.British journal of pharmacology · 2011Article
- Drug-induced long QT syndrome.Pharmacological reviews · 2010Review
- Safety profile of the fluoroquinolones: focus on levofloxacin.Drug safety · 2010Review
- Aurora kinase inhibitors: novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemias.Leukemia · 2010Review
- An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk.British journal of pharmacology · 2010Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.
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