ArticleNature communications2017
An allosteric ligand-binding site in the extracellular cap of K2P channels.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Light-induced analgesia provides a drug-free optical method for pain relief via activation of TRAAK kNature communications · 2026Article
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- Mapping the knowledge of epilepsy and Potassium Channels: A scientometric analysis in CiteSpace and VOSviewer.IBRO neuroscience reports · 2025Article
- TREK-1 and epilepsy: regulating the balance of KBehavioral and brain functions : BBF · 2025Review
- Altered synaptic homeostasis: a key factor in the pathophysiology of depression.Cell & bioscience · 2025Review
- Tick-Derived Peptide Blocks Potassium Channel TREK-1.International journal of molecular sciences · 2024Article
- Microglia as a Game Changer in Epilepsy Comorbid Depression.Molecular neurobiology · 2024Review
- Protein-ligand binding affinity prediction with edge awareness and supervised attention.iScience · 2023Article
- ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.Acta pharmacologica Sinica · 2022Article
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Molecular dynamics: a powerful tool for studying the medicinal chemistry of ion channel modulators.RSC medicinal chemistry · 2021Review
- Negative Influence by the Force: Mechanically Induced Hyperpolarization via KInternational journal of molecular sciences · 2021Review
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- Lipid-protein forces predict conformational changes in a mechanosensitive channel.European biophysics journal : EBJ · 2021Article
- Genetic and pharmacological inhibition of two-pore domain potassium channel TREK-1 alters depression-related behaviors and neuronal plasticity in the hippocampus in mice.CNS neuroscience & therapeutics · 2021Article
- The Prostacyclin Analogue, Treprostinil, Used in the Treatment of Pulmonary Arterial Hypertension, is a Potent Antagonist of TREK-1 and TREK-2 Potassium Channels.Frontiers in pharmacology · 2021Article
- The Polysite Pharmacology of TREK KAdvances in experimental medicine and biology · 2021Article
- Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels.International journal of molecular sciences · 2020Article
- Effect of 158 herbal remedies on human TRPV1 and the two-pore domain potassium channels KCNK2, 3 and 9.Journal of traditional and complementary medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two-pore domain potassium (K2P) channels generate leak currents that are responsible for the maintenance of the resting membrane potential, and they are thus potential drug targets for treating diseases. Here, we identify N-(4-cholorphenyl)-N-(2-(3,4-dihydrosioquinolin-2(1H)-yl)-2-oxoethyl)methanesulfonamide (TKDC) as an inhibitor of the TREK subfamily, including TREK-1, TREK-2 and TRAAK channels. Using TKDC as a chemical probe, a study combining computations, mutagenesis and electrophysiology reveals a K2P allosteric ligand-binding site located in the extracellular cap of the channels. Molecular dynamics simulations suggest that ligand-induced allosteric conformational transitions lead to blockage of the ion conductive pathway. Using virtual screening approach, we identify other inhibitors targeting the extracellular allosteric ligand-binding site of these channels. Overall, our results suggest that the allosteric site at the extracellular cap of the K2P channels might be a promising drug target for these membrane proteins.TREKs are members of the two-pore domain potassium (K2P) channels, being important clinical targets. Here the authors identify inhibitors of K2P that bind to an allosteric site located in their extracellular cap, suggesting that it might be a promising drug target for these channels.
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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.