62* Investigational compound VX-770 potentiated multiple CFTR channel gating mutants in vitro

Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle.

Vx-770 (Ivacaftor), a Food and Drug Administration (FDA)-approved drug for clinical application to patients with cystic fibrosis (CF), shifts the paradigm from conventional symptomatic treatments to therapeutics directly tackling the root of the disease: functional defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by pathogenic mutations. The unde...

Ivacaftor potentiation of multiple CFTR channels with gating mutations.

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 proba...

Title: Synergistic Potentiation of CFTR gating by two chemically distinct potentiators, Ivacaftor (VX-770) and NPPB

Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in min...

Cftr Channel Gating

Two papers, one in this issue (Weinreich et al., 1999) and the other in the April issue of The Journal (Zelt-wanger et al., 1999), help clarify the gating mechanisms of cystic fibrosis transmembrane conductance regulator (CFTR) Cl Ϫ channels, the products of the gene found mutated in cystic fibrosis patients. CFTR is a most unusual ion channel. It is a prominent member of the ABC transporter su...