ArticleThe Journal of clinical investigation2002
Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 340 papers.
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Who cites it
340 citing papers in PubMed, 632 citations in OpenAlex.
- BEST4⁺ cells: a potential hub of intestinal ion transport and diarrhea manipulation.Advanced biotechnology · 2026Review
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Reconstitution of CFTR ubiquitination identifies lysine-420 as a regulator of cell surface residence and current.Biochemistry and biophysics reports · 2026Article
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Identification and pharmacological characterization of a natural folipastatin as a CFTR inhibitor and potential anti-secretory agent in a human colonoid model.BMC complementary medicine and therapies · 2025Article
- The natural statin α,β-dehydromonacolin K exerts anti-secretory effect in human intestinal epithelial cells via a nonsense-mediated mRNA decay-dependent mechanism.Pharmaceutical biology · 2025Article
- Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism.Nature communications · 2025Article
- The apical mucus layer alters the pharmacological properties of the airway epithelium.The Journal of physiology · 2025Article
- NLRP3 inflammasome in neuroinflammation and central nervous system diseases.Cellular & molecular immunology · 2025Review
- Role of Pannexin 1, P2X7, and CFTR in ATP Release and Autocrine Signaling by Principal Cells of the Epididymis.Function (Oxford, England) · 2025Article
- Esc peptides and derivatives potentiate the activity of CFTR with gating defects and display antipseudomonal activity in cystic fibrosis-like lung disease.Cellular and molecular life sciences : CMLS · 2025Article
- Matrix-free human 2D organoids recapitulate duodenal barrier and transport properties.BMC biology · 2025Article
- Yellow Fluorescent Protein Quenching Assay for Analyzing Odorant Receptor Activity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.The European respiratory journal · 2025Article
- Alternative splicing and residual function potentially expand the therapeutic landscape of the CFTRdele2ins182 variant.PloS one · 2025Article
- Inhibiting CFTR through inh-172 in primary neutrophils reveals CFTR-specific functional defects.Scientific reports · 2024Article
- Tunable Cytosolic Chloride Indicators for Real-Time Chloride Imaging in Live Cells.bioRxiv : the preprint server for biology · 2024Article
- Allosteric inhibition of CFTR gating by CFTRinh-172 binding in the pore.Nature communications · 2024Article
- DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function.JCI insight · 2024Article
- Key role of down-regulated in adenoma (bioRxiv : the preprint server for biology · 2024Article
280 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Secretory diarrhea is the leading cause of infant death in developing countries and a major cause of morbidity in adults. The cystic fibrosis transmembrane conductance regulator (CFTR) protein is required for fluid secretion in the intestine and airways and, when defective, causes the lethal genetic disease cystic fibrosis. We screened 50,000 chemically diverse compounds for inhibition of cAMP/flavone-stimulated Cl(-) transport in epithelial cells expressing CFTR. Six CFTR inhibitors of the 2-thioxo-4-thiazolidinone chemical class were identified. The most potent compound discovered by screening of structural analogs, CFTR(inh)-172, reversibly inhibited CFTR short-circuit current in less than 2 minutes in a voltage-independent manner with K(I) approximately 300 nM. CFTR(inh)-172 was nontoxic at high concentrations in cell culture and mouse models. At concentrations fully inhibiting CFTR, CFTR(inh)-172 did not prevent elevation of cellular cAMP or inhibit non-CFTR Cl(-) channels, multidrug resistance protein-1 (MDR-1), ATP-sensitive K(+) channels, or a series of other transporters. A single intraperitoneal injection of CFTR(inh)-172 (250 micro g/kg) in mice reduced by more than 90% cholera toxin-induced fluid secretion in the small intestine over 6 hours. Thiazolidinone CFTR inhibitors may be useful in developing large-animal models of cystic fibrosis and in reducing intestinal fluid loss in cholera and other secretory diarrheas.
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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.