Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of in Vitro Pharmacology and Clinical Translation
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Abstract
Pharmacological correction of the defective ion channel with cystic fibrosis transmembrane
conductance regulator (CFTR) has become an attractive approach to therapy directed
at the root cause of the life-limiting disease cystic fibrosis (CF). CFTR defects
range from absence, misfolding, and resulting degradation to functional defects of
the CFTR protein. The discovery and development of the CFTR potentiator ivacaftor
was a major break-through in CF therapy and has triggered an enormous incentive for
seeking effective modulators such as lumacaftor, tezacaftor or elexacaftor for all
patients with CF. A number of emerging CFTR modulators are currently in the development
pipeline, and rescue levels of CFTR protein approach a cure for cystic fibrosis. In
this review, we identify and characterize all preclinical and clinical emerging CFTR
modulators and discuss the in vitro pharmacology, looking at CFTR protein expression
and chloride transport and the translation to the clinic. The new emerging CFTR modulators
could offer new therapeutic solutions for CF patients.
[1
]Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty
of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville,
Victoria 3010, Australia