{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:24:16Z","timestamp":1793057056347,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,3]]},"abstract":"<jats:p>\n                    Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A (PKA)-activated epithelial anion channel involved in salt and fluid transport in multiple organs, including the lung. Most CF mutations either reduce the number of CFTR channels at the cell surface (e.g., synthesis or processing mutations) or impair channel function (e.g., gating or conductance mutations) or both. There are currently no approved therapies that target CFTR. Here we describe the in vitro pharmacology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of CF. In recombinant cells VX-770 increased CFTR channel open probability (P\n                    <jats:sub>o<\/jats:sub>\n                    ) in both the F508del processing mutation and the G551D gating mutation. VX-770 also increased Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by \u224810-fold, to \u224850% of that observed in HBE isolated from individuals without CF. Furthermore, VX-770 reduced excessive Na\n                    <jats:sup>+<\/jats:sup>\n                    and fluid absorption to prevent dehydration of the apical surface and increased cilia beating in these epithelial cultures. These results support the hypothesis that pharmacological agents that restore or increase CFTR function can rescue epithelial cell function in human CF airway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0904709106","type":"journal-article","created":{"date-parts":[[2009,10,21]],"date-time":"2009-10-21T22:12:20Z","timestamp":1256163140000},"page":"18825-18830","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1167,"title":["Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770"],"prefix":"10.1073","volume":"106","author":[{"given":"Fredrick","family":"Van Goor","sequence":"first","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Hadida","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D. 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Ashlock","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Foundation Therapeutics, Inc., 6931 Arlington Road, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Negulescu","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2570460"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115450"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110894"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28463"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/301421a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5340"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70344-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.05.001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512766200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81724-9"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200304-505SO"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90353-R"},{"key":"e_1_3_3_14_2","first-page":"29","article-title":"Pharmacological rescue of mutant CFTR funciton for the treatment of cystic fibrosis","volume":"3","author":"Van Goor F","year":"2008","unstructured":"F Van Goor, S Hadida, PDJ Grootenhuis, Pharmacological rescue of mutant CFTR funciton for the treatment of cystic fibrosis. 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