ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 55 citations in OpenAlex.
- Human Nasal and Bronchial Epithelium in Cystic Fibrosis: Differences in Expression of Airway pH Regulatory Proteins.Pediatric pulmonology · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- The comparison of two pendrin inhibitors, YS-01 and PDSinh-C01, in lipopolysaccharide-induced acute lung injury.Scientific reports · 2026Article
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Repurposing approved drugs as Pendrin (Frontiers in pharmacology · 2026Article
- High potency 3-carboxy-2-methylbenzofuran pendrin inhibitors as novel diuretics.European journal of medicinal chemistry · 2025Article
- Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024Article
- Chloride/Multiple Anion Exchanger SLC26A Family: Systemic Roles of SLC26A4 in Various Organs.International journal of molecular sciences · 2024Review
- Pendrin: linking acid base to blood pressure.Pflugers Archiv : European journal of physiology · 2024Review
- Mechanism of anion exchange and small-molecule inhibition of pendrin.Nature communications · 2024Article
- CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.Frontiers in physiology · 2024Review
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- Review
- Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action.European journal of medicinal chemistry · 2023Article
- Airway surface hyperviscosity and defective mucociliary transport by IL-17/TNF-α are corrected by β-adrenergic stimulus.JCI insight · 2022Article
- Regulation of Blood Pressure and Salt Balance By Pendrin-Positive Intercalated Cells: Donald Seldin Lecture 2020.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Chloride transport modulators as drug candidates.American journal of physiology. Cell physiology · 2021Review
- SLC26A6-selective inhibitor identified in a small-molecule screen blocks fluid absorption in small intestine.JCI insight · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pendrin (SLC26A4) is a Cl(-)/anion exchanger expressed in the epithelium of inflamed airways where it is thought to facilitate Cl(-) absorption and HCO3 (-) secretion. Studies using pendrin knockout mice and airway epithelial cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic fibrosis (CF), perhaps by regulation of airway surface liquid (ASL) volume. Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in increasing ASL volume. A cell-based, functional high-throughput screen of ∼36,000 synthetic small molecules produced 3 chemical classes of inhibitors of human pendrin. After structure-activity studies, tetrahydropyrazolopyridine and pyrazolothiophenesulfonamide compounds reversibly inhibited pendrin-facilitated Cl(-) exchange with SCN(-), I(-), NO3 (-), and HCO3 (-) with drug concentration causing 50% inhibition down to ∼2.5 μM. In well-differentiated primary cultures of human airway epithelial cells from non-CF and CF subjects, treatment with IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl(-)/HCO3 (-) exchange and the increase was blocked by pendrin inhibition. Pendrin inhibition significantly increased ASL depth (by ∼8 μm) in IL-13-treated non-CF and CF cells but not in untreated cells. These studies implicate the involvement of pendrin-facilitated Cl(-)/HCO3 (-) in the regulation of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, including CF.-Haggie, P. M., Phuan, P.-W., Tan, J.-A., Zlock, L., Finkbeiner, W. E., Verkman, A. S. Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.
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Registered trials
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