ArticleChemistry & biology2012
A designed inhibitor of a CLC antiporter blocks function through a unique binding mode.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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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.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- Screening for bilayer-active and likely cytotoxic molecules reveals bilayer-mediated regulation of cell function.The Journal of general physiology · 2023Article
- Streptolysin S targets the sodium-bicarbonate cotransporter NBCn1 to induce inflammation and cytotoxicity in human keratinocytes during Group A Streptococcal infection.Frontiers in cellular and infection microbiology · 2022Article
- Proteomic Analysis of the Functional Inward Rectifier Potassium Channel (Kir) 2.1 Reveals Several Novel Phosphorylation Sites.Biochemistry · 2021Article
- β2-adrenergic Agonists Rescue Lysosome Acidification and Function in PSEN1 Deficiency by Reversing Defective ER-to-lysosome Delivery of ClC-7.Journal of molecular biology · 2020Article
- Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase.Scientific reports · 2019Article
- Best practices and benchmarks for intact protein analysis for top-down mass spectrometry.Nature methods · 2019Review
- Article
- Multiscale Kinetic Modeling Reveals an Ensemble of ClJournal of the American Chemical Society · 2018Article
- Divergent effects of anesthetics on lipid bilayer properties and sodium channel function.European biophysics journal : EBJ · 2017Review
- Instant Integrated Ultradeep Quantitative-structural Membrane Proteomics Discovered Post-translational Modification Signatures for Human Cys-loop Receptor Subunit Bias.Molecular & cellular proteomics : MCP · 2016Article
- Atomic-level description of protein-lipid interactions using an accelerated membrane model.Biochimica et biophysica acta · 2016Review
- Revealing an outward-facing open conformational state in a CLC Cl(-)/H(+) exchange transporter.eLife · 2016Article
- The Use of Advanced Mass Spectrometry to Dissect the Life-Cycle of Photosystem II.Frontiers in plant science · 2016Review
- Identification of a proton-chloride antiporter (EriC) by Himar1 transposon mutagenesis in Lactobacillus reuteri and its role in histamine production.Antonie van Leeuwenhoek · 2014Article
- Novel diuretic targets.American journal of physiology. Renal physiology · 2013Review
- Integral membrane proteins and bilayer proteomics.Analytical chemistry · 2013Review
- Surprises from an unusual CLC homolog.Biophysical journal · 2012Article
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
The lack of small-molecule inhibitors for anion-selective transporters and channels has impeded our understanding of the complex mechanisms that underlie ion passage. The ubiquitous CLC "Chloride Channel" family represents a unique target for biophysical and biochemical studies because its distinctive protein fold supports both passive chloride channels and secondary-active chloride-proton transporters. Here, we describe the synthesis and characterization of a specific small-molecule inhibitor directed against a CLC antiporter (ClC-ec1). This compound, 4,4'-octanamidostilbene-2,2'-disulfonate (OADS), inhibits ClC-ec1 with low micromolar affinity and has no specific effect on a CLC channel (ClC-1). Inhibition of ClC-ec1 occurs by binding to two distinct intracellular sites. The location of these sites and the lipid dependence of inhibition suggest potential mechanisms of action. This compound will empower research to elucidate differences between antiporter and channel mechanisms and to develop treatments for CLC-mediated disorders.
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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.