ReviewBritish journal of pharmacology2010
An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk.
Review in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Evaluation of the potential for QTc prolongation with avelumab.Cancer chemotherapy and pharmacology · 2019Pooled it
- Model-based evaluation of drug-induced QTc prolongation for compounds in early development.British journal of clinical pharmacology · 2015Trial
- Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2.British journal of pharmacology · 2012Trial
- New approach methodologies: drug screening platform to identify antifibrotic compounds.Nature protocols · 2026Review
- Exploring the Role of Metabolites in Torsadogenic Risk Assessment: A Text-Mining Approach.Turkish journal of pharmaceutical sciences · 2026Article
- A comprehensive review of 20 years of progress in nonclinical QT evaluation and proarrhythmic assessment.Journal of pharmacokinetics and pharmacodynamics · 2025Review
- Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort.Environmental health : a global access science source · 2024Article
- Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort.Research square · 2024Article
- Article
- Acute exposure to low-dose bisphenol A delays cardiac repolarization in female canine heart - Implication for proarrhythmic toxicity in large animals.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- An Extensive Metabolomics Workflow to Discover Cardiotoxin-Induced Molecular Perturbations in Microtissues.Metabolites · 2021Article
- Sex-specific IHeart rhythm · 2021Article
- A structure-based computational workflow to predict liability and binding modes of small molecules to hERG.Scientific reports · 2020Article
- Safety assessment of metarrestin in dogs: A clinical candidate targeting a subnuclear structure unique to metastatic cancer cells.Regulatory toxicology and pharmacology : RTP · 2020Article
- Transgenic Rabbit Models in Proarrhythmia Research.Frontiers in pharmacology · 2020Review
- Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia.MedChemComm · 2019Article
- Molecular Docking Guided Grid-Independent Descriptor Analysis to Probe the Impact of Water Molecules on Conformational Changes of hERG Inhibitors in Drug Trapping Phenomenon.International journal of molecular sciences · 2019Article
- On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships.Scientific reports · 2019Article
- Increased mesodermal and mesendodermal populations by BMP4 treatment facilitates human iPSC line differentiation into a cardiac lineage.Journal of stem cells & regenerative medicine · 2019Article
- A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation.Journal of pharmacokinetics and pharmacodynamics · 2018Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Owing to its association with Torsades de Pointes, drug-induced QT interval prolongation has been and remains a significant hurdle to the development of safe, effective medicines. Genetic and pharmacological evidence highlighting the pivotal role the human ether-a-go-go-related gene (hERG) channel was a critical step in understanding how to start addressing this issue. It led to the development of hERG assays with the rapid throughput needed for the short timescales required in early drug discovery. The resulting volume of hERG data has fostered in silico models to help chemists design compounds with reduced hERG potency. In early drug discovery, a pragmatic approach based on exceeding a given potency value has been required to decide when a compound is likely to carry a low QT risk, to support its progression to late-stage discovery. At this point, the in vivo efficacy and metabolism characteristics of the potential drug are generally defined, as well its safety profile, which includes usually a dog study to assess QT interval prolongation risk. The hERG and in vivo QT data, combined with the likely indication and the estimated free drug level for efficacy, are put together to assess the risk that the potential drug will prolong QT in man. Further data may be required to refine the risk assessment before making the major investment decisions for full development. The non-clinical data are essential to inform decisions about compound progression and to optimize the design of clinical QT studies.
Indexed as
Identifiers
What OpenQuestion holds
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.