{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:05Z","timestamp":1789448585770,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Type-2 airway inflammation remodels the airway epithelium and drives mucus-associated transcriptional programs, making the epithelium an attractive source of drug targets in allergic asthma. Reanalyzing GSE193816, a lower-airway single-cell RNA-seq dataset of allergic asthma (AA) and allergic non-asthma control (AC) participants sampled before and after allergen challenge, a systematic epithelial prioritization ranked\n                    <jats:italic>SLC26A4<\/jats:italic>\n                    \/Pendrin highly among asthma-enriched candidates, consistent with its previously reported induction in asthmatic airway epithelium.\n                    <jats:italic>SLC26A4<\/jats:italic>\n                    was epithelial-biased, was strongest in allergen-challenged asthmatic epithelium, and co-varied with an IL-13\/mucus program. Building on this nomination, structure-based virtual screening of approved drugs against the niflumic-acid inhibitor pocket of the cryo-EM Pendrin structure (PDB 8SHC) prioritized six chemically diverse, asthma-unrelated candidates predicted to occupy the pocket. In a halide-flux assay using cells co-expressing Pendrin and a halide-sensitive YFP reporter, these drugs produced concentration-dependent, partial inhibition of Pendrin-mediated transport, with deferasirox and lemborexant the most efficacious and exceeding the niflumic-acid positive control. Because inhibition was partial and occurred at high-micromolar concentrations, these data are a preliminary\n                    <jats:italic>in vitro<\/jats:italic>\n                    observation, consistent with but not confirming a repurposing hypothesis for Pendrin in allergic asthma, rather than evidence of therapeutic benefit.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1926844","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:28:05Z","timestamp":1789446485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing approved drugs as Pendrin (SLC26A4) inhibitors in allergic asthma: single-cell nomination, structure-based screening and functional validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianxing","family":"Lai","sequence":"first","affiliation":[{"name":"Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duoduo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Information Science and Electronic Engineering, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binben","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Mathematical Sciences, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"eabq6352","DOI":"10.1126\/sciimmunol.abq6352","article-title":"A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma","volume":"8","author":"Alladina","year":"2023","journal-title":"Sci. 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