ArticleFrontiers in pharmacology2010
Stereoselective Inhibition of the hERG1 Potassium Channel.
Article in Frontiers in pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Clinical trials in a dish: cardiometabolic drug development with biological and digital twins.The Journal of clinical investigation · 2026Review
- Research progress on the relationship between long QT syndrome (LQTS) and epilepsy: A review.Medicine · 2026Review
- A comprehensive review of 20 years of progress in nonclinical QT evaluation and proarrhythmic assessment.Journal of pharmacokinetics and pharmacodynamics · 2025Review
- New Synthesis and Pharmacological Evaluation of Enantiomerically Pure (Journal of medicinal chemistry · 2025Article
- Stereoselective block of the hERG potassium channel by the Class Ia antiarrhythmic drug disopyramide.Cellular and molecular life sciences : CMLS · 2024Article
- Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone.Molecular psychiatry · 2024Article
- Dissimilar effects of stereoisomers and racemic hydroxychloroquine on CaPhysiological reports · 2023Article
- Molecular determinants of pro-arrhythmia proclivity of d- and l-sotalol via a multi-scale modeling pipeline.Journal of molecular and cellular cardiology · 2021Article
- Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity.ACS medicinal chemistry letters · 2020Article
- Inherited Cardiac Arrhythmia Syndromes: Focus on Molecular Mechanisms Underlying TRPM4 Channelopathies.Cardiovascular therapeutics · 2020Review
- [Proarrhythmic adverse effects of nonarrhythmic drugs].Herzschrittmachertherapie & Elektrophysiologie · 2019Review
- Evolution of strategies to improve preclinical cardiac safety testing.Nature reviews. Drug discovery · 2016Review
- Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise?Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2016Article
- ICH E14 Q&A(R2) document: commentary on the further updated recommendations on thorough QT studies.British journal of clinical pharmacology · 2015Article
- The opioid methadone induces a local anaesthetic-like inhibition of the cardiac Na⁺ channel, Na(v)1.5.British journal of pharmacology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1) channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom) is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.