{"doi":"10.17615/5abr-pa41","title":"Inositol polyphosphate derivative inhibits Na + transport and improves fluid dynamics in cystic fibrosis airway epithelia","abstract":"Amiloride-sensitive, epithelial Na+ channel (ENaC)-mediated, active absorption of Na+ is elevated in the airway epithelium of cystic fibrosis (CF) patients, resulting in excess fluid removal from the airway lumen. This excess fluid/volume absorption corresponds to CF transmembrane regulator-linked defects in ENaC regulation, resulting in the reduced mucociliary clearance found in CF airways. Herein we show that INO-4995, a synthetic analog of the intracellular signaling molecule, D-myo-inositol 3,4,5,6-tetrakisphosphate, inhibits Na+ and fluid absorption across CF airway epithelia, thus alleviating this critical pathology. This conclusion was based on electrophysiological studies, fluid absorption, and 22Na+ flux measurements in CF airway epithelia, contrasted with normal epithelia, and on electrophysiological studies in Madin-Darby canine kidney cells and 3T3 cells overexpressing ENaC. The effects of INO-4995 were long-lasting, dose-dependent, and more pronounced in epithelia from CF patients vs. controls. These findings support preclinical development of INO-4995 for CF treatment and demonstrate for the first time the therapeutic potential of inositol polyphosphate derivatives.","journal":"UNC Libraries","year":2020,"id":141445,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":394597,"name":"Alexis Traynor‐Kaplan","orcid":"0000-0002-0006-0543","position":1,"is_corresponding":false},{"id":607486,"name":"J. H. Widdicombe","orcid":null,"position":2,"is_corresponding":false},{"id":607487,"name":"Carlo Dinkel","orcid":null,"position":3,"is_corresponding":false},{"id":394598,"name":"Carsten Schultz","orcid":"0000-0002-5824-2171","position":4,"is_corresponding":false},{"id":607488,"name":"Carey Pennington","orcid":null,"position":5,"is_corresponding":false},{"id":523368,"name":"Sherif E. Gabriel","orcid":null,"position":6,"is_corresponding":false},{"id":607489,"name":"Ray A. Caldwell","orcid":null,"position":7,"is_corresponding":false},{"id":607490,"name":"Michael W. Rossi","orcid":null,"position":8,"is_corresponding":false},{"id":607491,"name":"Mark Moody","orcid":null,"position":9,"is_corresponding":false},{"id":289125,"name":"Sharon McNamara","orcid":"0000-0003-4895-3364","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:24.429854Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}