title: Breakthrough therapies: Cystic fibrosis (CF) potentiators and correctors.
abstract: Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators are also emphasized.
authors.affiliation: Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama.
authors.forename: George M
authors.initials: GM
authors.lastname: Solomon
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Marshall
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.|Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Ramsey
authors.affiliation: Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama.|Departments of Medicine, Pediatrics, Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000627:Aminophenols / Q000627:therapeutic use; D000631:Aminopyridines / Q000627:therapeutic use; D000818:Animals; D052117:Benzodioxoles / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D015195:Drug Design; D006720:Homozygote; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009154:Mutation; D017510:Protein Folding; D015363:Quinolones / Q000627:therapeutic use
chemical_list: D000627:Aminophenols; D000631:Aminopyridines; D052117:Benzodioxoles; C505032:CFTR protein, human; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; C569105:lumacaftor
keywords: CFTR modulators; CFTR molecular defect; cystic fibrosis; lung disease; novel therapies