ArticleToxicology and applied pharmacology2011
Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels.
Article in Toxicology and applied pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 42 citations in OpenAlex.
- Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R.Endocrinology · 2024Article
- Ketamine preservative benzethonium chloride potentiates hippocampal synaptic transmission and binds neurotransmitter receptors and transporters.Neuropharmacology · 2023Review
- High-Throughput Chemical Screening and Structure-Based Models to Predict hERG Inhibition.Biology · 2022Article
- Cell-Based hERG Channel Inhibition Assay in High-Throughput Format.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cardiotoxicity Hazard and Risk Characterization of ToxCast Chemicals Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes from Multiple Donors.Chemical research in toxicology · 2021Article
- Deep Graph Learning with Property Augmentation for Predicting Drug-Induced Liver Injury.Chemical research in toxicology · 2021Article
- Review of high-content screening applications in toxicology.Archives of toxicology · 2019Review
- Natural products modulating the hERG channel: heartaches and hope.Natural product reports · 2017Review
- Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data.Environmental health perspectives · 2017Article
- The Essential Medicinal Chemistry of Curcumin.Journal of medicinal chemistry · 2017Review
- Inhibition of HERG potassium channels by domiphen bromide and didecyl dimethylammonium bromide.European journal of pharmacology · 2014Article
- Identification of hepatic phospholipidosis inducers in sandwich-cultured rat hepatocytes, a physiologically relevant model, reveals altered basolateral uptake and biliary excretion of anionic probe substrates.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Identification of thyroid hormone receptor active compounds using a quantitative high-throughput screening platform.Current chemical genomics and translational medicine · 2014Article
- Are hERG channel blockers also phospholipidosis inducers?Bioorganic & medicinal chemistry letters · 2013Article
- Improving the human hazard characterization of chemicals: a Tox21 update.Environmental health perspectives · 2013Review
- Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride.Toxicology and applied pharmacology · 2013Article
- Paradigm shift in toxicity testing and modeling.The AAPS journal · 2012Review
- Profiling environmental chemicals for activity in the antioxidant response element signaling pathway using a high throughput screening approach.Environmental health perspectives · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The human ether-a-go-go-related gene (hERG) channel, a member of a family of voltage-gated potassium (K(+)) channels, plays a critical role in the repolarization of the cardiac action potential. The reduction of hERG channel activity as a result of adverse drug effects or genetic mutations may cause QT interval prolongation and potentially leads to acquired long QT syndrome. Thus, screening for hERG channel activity is important in drug development. Cardiotoxicity associated with the inhibition of hERG channels by environmental chemicals is also a public health concern. To assess the inhibitory effects of environmental chemicals on hERG channel function, we screened the National Toxicology Program (NTP) collection of 1408 compounds by measuring thallium influx into cells through hERG channels. Seventeen compounds with hERG channel inhibition were identified with IC(50) potencies ranging from 0.26 to 22μM. Twelve of these compounds were confirmed as hERG channel blockers in an automated whole cell patch clamp experiment. In addition, we investigated the structure-activity relationship of seven compounds belonging to the quaternary ammonium compound (QAC) series on hERG channel inhibition. Among four active QAC compounds, tetra-n-octylammonium bromide was the most potent with an IC(50) value of 260nM in the thallium influx assay and 80nM in the patch clamp assay. The potency of this class of hERG channel inhibitors appears to depend on the number and length of their aliphatic side-chains surrounding the charged nitrogen. Profiling environmental compound libraries for hERG channel inhibition provides information useful in prioritizing these compounds for cardiotoxicity assessment in vivo.
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.