title: Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function.
abstract: BACKGROUND
  Ivacaftor (KALYDECO™, VX-770) is a CFTR potentiator that increased CFTR channel activity and improved lung function in patients age 6 years and older with CF who have the G551D-CFTR gating mutation. The aim of this in vitro study was to evaluate the effect of ivacaftor on mutant CFTR protein forms with defects in protein processing and/or channel function.
  
  
  METHODS
  The effect of ivacaftor on CFTR function was tested in electrophysiological studies using a panel of Fischer rat thyroid (FRT) cells expressing 54 missense CFTR mutations that cause defects in the amount or function of CFTR at the cell surface.
  
  
  RESULTS
  Ivacaftor potentiated multiple mutant CFTR protein forms that produce functional CFTR at the cell surface. These included mutant CFTR forms with mild defects in CFTR processing or mild defects in CFTR channel conductance.
  
  
  CONCLUSIONS
  These in vitro data indicated that ivacaftor is a broad acting CFTR potentiator and could be used to help stratify patients with CF who have different CFTR genotypes for studies investigating the potential clinical benefit of ivacaftor.
authors.affiliation: Vertex Pharmaceuticals Incorporated, 130 Waverly St, Cambridge, MA, United States; Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, United States. Electronic address: fredrick_vangoor@sd.vrtx.com.
authors.forename: Fredrick
authors.initials: F
authors.lastname: Van Goor
authors.affiliation: Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, United States.
authors.forename: Haihui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, United States.
authors.forename: Bill
authors.initials: B
authors.lastname: Burton
authors.affiliation: Vertex Pharmaceuticals Incorporated, 11010 Torreyana Road, San Diego, CA 92121, United States.
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Hoffman
mesh_terms: D000627:Aminophenols / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects* / Q000235:genetics; D020125:Mutation, Missense; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000166:cytology
chemical_list: D000627:Aminophenols; C579654:CFTR protein, rat; D002712:Chlorides; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR; Ivacaftor; Potentiator; VX-770