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CFTR

Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR

3 views | Nov 12 2019

Loo TW et al. suggested that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. [Read the Full Post]

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

20 views | Sep 29 2019

Veit G et al. indicated that VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. [Read the Full Post]

Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation

147 views | Jan 18 2019

Accurso FJ et al. evaluated the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. [Read the Full Post]

Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

167 views | Jan 17 2019

Rowe SM et al. showed that CFTR modulator therapy with tezacaftor-ivacaftor or ivacaftor alone was efficacious in patients with cystic fibrosis who were heterozygous for the Phe508del deletion and a CFTR residual-function mutation. [Read the Full Post]

CFTR protects against vascular inflammation and atherogenesis in apolipoprotein E-deficient mice

135 views | Jan 08 2019

Li Z et al. suggested that CFTR may present a potential therapeutic target for the treatment of vascular inflammation and development of atherosclerotic disease. [Read the Full Post]

High-expressing cystic fibrosis transmembrane conductance regulator interacts with histone deacetylase 2 to promote the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway

0 views | Oct 04 2018

Yan T et al. provides strong evidence that high-expression CFTR plays an important role in the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway. [Read the Full Post]

Tissue-specific variation in nonsense mutant transcript level and drug-induced read-through efficiency in the Cln1(R151X) mouse model of INC

550 views | Nov 22 2017

Thada V et al. identified a new challenge/hurdle for read-through drug therapy: variable efficiency of read-through therapy in the different tissues/organs because of tissue-specific variations in nonsense mutant transcript levels. [Read the Full Post]

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

0 views | Oct 15 2017

Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]

Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis

620 views | Oct 14 2017

Bali V et al. emphasized that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

798 views | Oct 04 2017

Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]