Nanomolar-potency ‘co-potentiator’ therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants

• Published in: Scientific reports Vol. 9; no. 1; pp. 17640 - 12
• Main Authors: Phuan, Puay-Wah, Tan, Joseph-Anthony, Rivera, Amber A., Zlock, Lorna, Nielson, Dennis W., Finkbeiner, Walter E., Haggie, Peter M., Verkman, Alan S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.11.2019; Nature Publishing Group
• Subjects: 631/154; 631/45/269/1147; Cell culture; Chloride conductance; Clonal deletion; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis - metabolism; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Drug Discovery; Drug Synergism; Epithelial cells; Gene deletion; High-Throughput Screening Assays; Humanities and Social Sciences; Humans; multidisciplinary; Mutation; Piperidine; Piperidines - therapeutic use; Pyrazoles - therapeutic use; Science; Science (multidisciplinary); Structure-Activity Relationship

Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of ‘co-potentiators’ (combination-pot...