title: Ivacaftor potentiation of multiple CFTR channels with gating mutations.
abstract: BACKGROUND
  The investigational CFTR potentiator ivacaftor (VX-770) increased CFTR channel activity and improved lung function in subjects with CF who have the G551D CFTR gating mutation. The aim of this in vitro study was to determine whether ivacaftor potentiates mutant CFTR with gating defects caused by other CFTR gating mutations.
  
  
  METHODS
  The effects of ivacaftor on CFTR channel open probability and chloride transport were tested in electrophysiological studies using Fischer rat thyroid (FRT) cells expressing different CFTR gating mutations.
  
  
  RESULTS
  Ivacaftor potentiated multiple mutant CFTR forms with defects in CFTR channel gating. These included the G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P and G1349D CFTR gating mutations.
  
  
  CONCLUSIONS
  These in vitro data suggest that ivacaftor has a similar effect on all CFTR forms with gating defects and support investigation of the potential clinical benefit of ivacaftor in CF patients who have CFTR gating mutations beyond G551D.
authors.affiliation: Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139, USA.
authors.forename: Haihui
authors.initials: H
authors.lastname: Yu
authors.forename: Bill
authors.initials: B
authors.lastname: Burton
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Huang
authors.forename: Jennings
authors.initials: J
authors.lastname: Worley
authors.forename: Dong
authors.initials: D
authors.lastname: Cao
authors.forename: James P
authors.initials: JP
authors.lastname: Johnson
authors.forename: Art
authors.initials: A
authors.lastname: Urrutia
authors.forename: John
authors.initials: J
authors.lastname: Joubran
authors.forename: Sheila
authors.initials: S
authors.lastname: Seepersaud
authors.forename: Katherine
authors.initials: K
authors.lastname: Sussky
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Hoffman
authors.forename: Fredrick
authors.initials: F
authors.lastname: Van Goor
mesh_terms: D000627:Aminophenols / Q000627:therapeutic use*; D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D015640:Ion Channel Gating / Q000235:genetics; D017136:Ion Transport / Q000235:genetics; D009154:Mutation / Q000187:drug effects*; D011379:Prognosis; D015363:Quinolones / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology
chemical_list: D000627:Aminophenols; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D004247:DNA