ArticleNature chemical biology2013
Side pockets provide the basis for a new mechanism of Kv channel-specific inhibition.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 59 citations in OpenAlex.
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- Rational design, synthesis, and evaluation of novel polypharmacological compounds targeting NaThe Journal of biological chemistry · 2025Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- Inhibitory Effects of 2-Aminoethoxydiphenyl Borate (2-APB) on Three KMolecules (Basel, Switzerland) · 2023Article
- Inhibition of NMDA receptors through a membrane-to-channel path.Nature communications · 2022Article
- Common Structural Pattern for Flecainide Binding in Atrial-Selective KPharmaceutics · 2022Article
- A small-molecule Psora-4 acts as a caloric restriction mimetic to promote longevity in C. elegans.GeroScience · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant.Cellular and molecular life sciences : CMLS · 2021Article
- Discovery of KMedicinal research reviews · 2021Review
- Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family.Redox biology · 2020Article
- Hydrophobic Drug/Toxin Binding Sites in Voltage-Dependent KFrontiers in pharmacology · 2020Review
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- Article
- Computational Study of the Loss-of-Function Mutations in the Kv1.5 Channel Associated with Atrial Fibrillation.ACS omega · 2018Article
- Predicting Structural Details of the Sodium Channel Pore Basing on Animal Toxin Studies.Frontiers in pharmacology · 2018Review
- Molecular determinants of beta-adrenergic signaling to voltage-gated KMicrocirculation (New York, N.Y. : 1994) · 2018Review
- A drug pocket at the lipid bilayer-potassium channel interface.Science advances · 2017Article
- Angiotensin II reduces the surface abundance of KThe Journal of physiology · 2017Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Most known small-molecule inhibitors of voltage-gated ion channels have poor subtype specificity because they interact with a highly conserved binding site in the central cavity. Using alanine-scanning mutagenesis, electrophysiological recordings and molecular modeling, we have identified a new drug-binding site in Kv1.x channels. We report that Psora-4 can discriminate between related Kv channel subtypes because, in addition to binding the central pore cavity, it binds a second, less conserved site located in side pockets formed by the backsides of S5 and S6, the S4-S5 linker, part of the voltage sensor and the pore helix. Simultaneous drug occupation of both binding sites results in an extremely stable nonconducting state that confers high affinity, cooperativity, use-dependence and selectivity to Psora-4 inhibition of Kv1.x channels. This new mechanism of inhibition represents a molecular basis for the development of a new class of allosteric and selective voltage-gated channel inhibitors.
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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.