{"doi":"10.1183/09059180.00008412","title":"Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis","abstract":"<jats:p>Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the<jats:italic>CFTR</jats:italic>gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target<jats:italic>CFTR</jats:italic>mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-<jats:italic>CFTR</jats:italic>mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.</jats:p>","journal":"European Respiratory Review","year":2013,"id":618706,"datarank":0.7218276533058626,"base_score":4.812184355372417,"endowment":4.812184355372417,"self_citation_contribution":0.7218276533058626,"citation_network_contribution":0.0,"self_endowment_contribution":0.7218276533058626,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":122,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1596310,"name":"Nico Derichs","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis","abstract":"<jats:p>Cystic fibrosis (CF) is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR) protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the<jats:italic>CFTR</jats:italic>gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target<jats:italic>CFTR</jats:italic>mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-<jats:italic>CFTR</jats:italic>mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.</jats:p>","is_dataset_classified":null,"base_score":4.812184355372417,"endowment":4.812184355372417,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23457166","pmcid":"PMC9487424","openalex_id":"https://openalex.org/W2135446403","authors":[],"funders":[],"total_grants":0,"fwci":9.8226,"citation_percentile":0.98604645,"influential_citations":0,"citation_trend":[{"year":2013,"count":11},{"year":2014,"count":16},{"year":2015,"count":12},{"year":2016,"count":6},{"year":2017,"count":13},{"year":2018,"count":5},{"year":2019,"count":3},{"year":2020,"count":12},{"year":2021,"count":12},{"year":2022,"count":4},{"year":2023,"count":10},{"year":2024,"count":12},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-sa","oa_locations":[{"url":"https://doi.org/10.1183/09059180.00008412","host_type":"journal"},{"url":"https://doi.org/10.1183/09059180.00008412","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1183/09059180.00008412","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23457166","host_type":"repository"},{"url":"https://doaj.org/article/03f812376f2d488ca1e6af654a08d6f6","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9487424","host_type":"repository"}],"fields_of_study":["Cystic Fibrosis Research Advances","Neonatal Respiratory Health Research","Congenital Ear and Nasal Anomalies","Aminophenols","Animals","Cystic Fibrosis","Cystic Fibrosis Transmembrane Conductance Regulator","Drug Discovery","Genetic Predisposition to Disease","Genetic Therapy","High-Throughput Screening Assays","Humans","Molecular Targeted Therapy","Mutation","Phenotype","Precision Medicine","Prognosis","Protein Conformation","Quinolones","Respiratory System Agents","Structure-Activity Relationship"],"mesh_terms":["Aminophenols","Animals","Cystic Fibrosis","Humans","Mutation","Phenotype","Prognosis","Protein Conformation","Structure-Activity Relationship","Genetic Therapy","Quinolones","Cystic Fibrosis Transmembrane Conductance Regulator","Respiratory System Agents","Genetic Predisposition to Disease","Drug Discovery","High-Throughput Screening Assays","Precision Medicine","Molecular Targeted Therapy"],"keywords":["Ivacaftor","Cystic fibrosis","Cystic fibrosis transmembrane conductance regulator","Potentiator","Medicine","Chloride channel","Mutation","Genetic enhancement","Gating","Pharmacology","Cancer research","Bioinformatics","Cell biology","Gene","Internal medicine","Biology","Genetics","Physiology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T05:03:24.391967Z","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":[]}