Cystic fibrosis is a progressive, lethal, recessive genetic disease. Cystic fibrosis is caused by mutations affecting the CFTR gene localized on chromosome 7, which encodes a cAMPdependent chloride channel located at the apical membrane of epithelial cells in several tissues. CFTR belongs to the ATP-binding cassette (ABC) transporter family and works as a channel for small anions, such as chloride and bicarbonate. Moreover, CFTR consists of two homologous halves, each comprising a transmembrane (TMD) and a nucleotide binding domain (NBD). Especially, Mutations of the CFTR gene affecting chloride ion channel function lead to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis.

Elexacaftor (previously known as VX-445) is a next-generation and orally active cystic fibrosis transmembrane conductance regulator (CFTR) corrector. This compound acts at a different site, facilitates the processing and trafficking of CFTR to increase the amount of CFTR at the cell surface. Elexacaftor, co-administered with Tezacaftor and Ivacaftor (Elexacaftor-Tezacaftor-Ivacaftor), which has the potential for cystic fibrosis research. In vitro, Elexacaftor-Tezacaftor-Ivacaftor significantly improves Phe508del CFTR protein processing, trafficking, and chloride transport. In addition, Elexacaftor increases the expression of mature CFTR protein in a culture of human bronchial epithelial cells derived from p.Phe508del mutation (F/F) and p.Phe508del and a minimal function mutation (F/MF) donors with cystic fibrosis.

To sum up, Elexacaftor is a next-generation and orally active CFTR corrector, which has the potential for cystic fibrosis research.


[1] Dominic Keating, et al. N Engl J Med. 2018 Oct 25;379(17):1612-1620. 

[2] Andrea Gramegna, et al. Curr Opin Pharmacol. 2021 Apr;57:81-88.