Current development of CFTR potentiators in the last decade

Cystic fibrosis (CF) is a genetic disorder produced by the loss of function of CFTR, a main chloride channel involved in transepithelial salt and water transport. CFTR function can be rescued by small molecules called “potentiators” which increase gating activity of CFTR on epithelial surfaces. High...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2020-10, Vol.204, p.112631-112631, Article 112631
Main Authors: Spanò, Virginia, Venturini, Arianna, Genovese, Michele, Barreca, Marilia, Raimondi, Maria Valeria, Montalbano, Alessandra, Galietta, Luis J.V., Barraja, Paola
Format: Article
Language:English
Subjects:
CFTR
CFTR potentiators
Cystic fibrosis
Cystic fibrosis transmembrane conductance regulator
VX-770
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Summary:Cystic fibrosis (CF) is a genetic disorder produced by the loss of function of CFTR, a main chloride channel involved in transepithelial salt and water transport. CFTR function can be rescued by small molecules called “potentiators” which increase gating activity of CFTR on epithelial surfaces. High throughput screening (HTS) assays allowed the identification of new chemical entities endowed with potentiator properties, further improved through medicinal chemistry optimization. In this review, the most relevant classes of CFTR potentiators developed in the last decade were explored, focusing on structure-activity relationships (SAR) of the different chemical entities, as a useful tool for the improvement of their pharmacological activity. [Display omitted] •Cystic fibrosis is a genetic disease caused by mutations of the CFTR gene.•Potentiators restore the physiological mechanism leading to CFTR activation.•Structural requirements to increase potentiator activity are explored.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2020.112631