Cystic fibrosis associated liver disease in children

Table 8 Cystic fibrosis transmembrane conductance regulator modulators

Type of modulator	Mechanism of action	Mutation class in which drug is effective	Example	Clinical effects/present status of modulator
Potentiators	Restore or even enhance the channel open probability, thus allowing for CFTR-dependent anion conductance	Classes III and IV	Ivacaftor	Improvement in lung function, pancreatic function and body mass index
Correctors	Rescue folding, processing and trafficking to the plasma membrane of a CFTR mutant. Enhance protein conformational stability during the endoplasmic reticulum folding process	Class II	Lumacaftor; Tezacaftor; Posenacaftor; Elexacaftor	Significant improvement in lung function when used with Ivacaftor
Stabilizers	Anchor CFTR at the plasma membrane, thus preventing its removal and degradation by lysosomes	Class VI	Cavosonstat	First CFTR stabilizer studied in clinical trials- studies terminated because of lack of clinical efficacy
Read-through agents	Induce ribosomal over-reading of premature termination codon, enabling the incorporation of a foreign amino acid in place and continued translation to the normal end of the transcript	Class I	Ataluren (PTC124)	Clinical trials terminated
Amplifiers	Increase expression of CFTR mRNA and thus biosynthesis of the CFTR protein	Class V	Nesolicaftor (PTI-428)	Clinical trial planned

CFTR: Cystic fibrosis transmembrane conductance regulator; mRNA: Messenger RNA.