ArticleNature communications2012
Identification of the functional binding pocket for compounds targeting small-conductance Ca²⁺-activated potassium channels.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 70 citations in OpenAlex.
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Structural mechanisms for inhibition and activation of human small-conductance CaNature communications · 2026Article
- Structural basis for the subtype-selectivity of KNature communications · 2026Article
- 6,7-Dichloro-1H-indole-2,3-dione-3-oxime functions as a superagonist for the intermediate-conductance CaMolecular pharmacology · 2025Article
- Molecular Glue Discovery: Current and Future Approaches.Journal of medicinal chemistry · 2023Review
- Protein-protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction.RSC chemical biology · 2023Review
- Article
- Allosteric inhibitors targeting the calmodulin-PIP2 interface of SK4 KProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Subtype-selective positive modulation of KBritish journal of pharmacology · 2022Article
- Ionic Channels as Potential Targets for the Treatment of Autism Spectrum Disorder: A Review.Current neuropharmacology · 2022Review
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Differential modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
- Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent CaActa physiologica (Oxford, England) · 2021Article
- Molecular Choreography and Structure of CaMembranes · 2020Review
- Atomistic Insights of Calmodulin Gating of Complete Ion Channels.International journal of molecular sciences · 2020Review
- Activation of small conductance calcium-activated potassium channels suppresses seizure susceptibility in the genetically epilepsy-prone rats.Neuropharmacology · 2020Article
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- Ionic Channels as Potential Therapeutic Targets for Erectile Dysfunction: A Review.Frontiers in pharmacology · 2020Review
- The Trials and Tribulations of Structure Assisted Design of KFrontiers in pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class.
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.