ArticleBritish journal of pharmacology2022
An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.
Article in British journal of pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Cardiosim-Tox: an interpretable multitask deep learning QSAR platform with multimodal feature fusion for predicting hERG, Cav1.2, and Nav1.5 blockade risk and potency.Archives of toxicology · 2026Article
- Real-time GPU-accelerated coupled cardiac system: Integrating bidirectional interactions between living optogenetic monolayers and computational simulations.PLoS computational biology · 2026Article
- Paired single-cell imaging of calcium and expression to map niches of identity and function.bioRxiv : the preprint server for biology · 2026Article
- Cardiotoxicity adverse outcome pathway network: towards mechanistic and quantitative modelling.Frontiers in toxicology · 2026Article
- The electrophysiology of ventricular cell pairs.Pflugers Archiv : European journal of physiology · 2025Review
- Resolving Artifacts in Voltage-Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.Nature communications · 2025Article
- Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights.The Journal of physiology · 2024Review
- Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments.The Journal of physiology · 2024Article
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.PLoS computational biology · 2024Article
- Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology.American journal of physiology. Heart and circulatory physiology · 2024Article
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.bioRxiv : the preprint server for biology · 2024Article
- The Dynamic Clamp Technique: A Robust Toolkit for Investigating Potassium Channel Function.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Emerging methods to model cardiac ion channel and myocyte electrophysiology.Biophysics reviews · 2023Review
- Correction to "An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic proarrhythmia mechanisms".British journal of pharmacology · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy.Handbook of experimental pharmacology · 2023Article
- Inhibitory Effects of Nobiletin on Voltage-Gated NaInternational journal of molecular sciences · 2022Article
- An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.British journal of pharmacology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
Abstract
background and purposeBefore advancing to clinical trials, new drugs are screened for their pro-arrhythmic potential using a method that is overly conservative and provides limited mechanistic insight. The shortcomings of this approach can lead to the mis-classification of beneficial drugs as pro-arrhythmic. EXPERIMENTAL APPROACH: An in silico-in vitro pipeline was developed to circumvent these shortcomings. A computational human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model was used as part of a genetic algorithm to design experiments, specifically electrophysiological voltage clamp (VC) protocols, to identify which of several cardiac ion channels were blocked during in vitro drug studies. Such VC data, along with dynamically clamped action potentials (AP), were acquired from iPSC-CMs before and after treatment with a control solution or a low- (verapamil), intermediate- (cisapride or quinine) or high-risk (quinidine) drug. KEY
resultsSignificant AP prolongation (a pro-arrhythmia marker) was seen in response to quinidine and quinine. The VC protocol identified block of I CONCLUSION AND IMPLICATIONS: We developed an in silico-in vitro pipeline that simultaneously identifies pro-arrhythmia risk and mechanism of ion channel-blocking drugs. The approach offers a new tool for evaluating cardiotoxicity during preclinical drug screening.
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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.