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.