The search for a common structural moiety among selected pharmacological correctors of the mutant CFTR chloride channel
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Updated: Apr 19, 2026

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Erika Nieddu1, Benedetta Pollarolo, Marco T Mazzei
1Department of Pharmacy, University of Genova, Viale Benedetto XV, 3 - 16132 Genova, Italy.
Background:
The F508del mutation impairs the trafficking of CFTR from endoplasmic reticulum to plasma membrane and is responsible of a severe form of cystic fibrosis. Trafficking can be improved by small organic molecules called 'correctors'.
Materials & Methods:
By different synthetic ways, we prepared 4-chloroanisole and 2-(4-chloroanisol-2-yl)aminothiazole derivatives. Such compounds were ineffective as correctors but we could find a sign of activity in an intermediate. In the meantime, we found a common pharmacophoric moiety present in four known correctors.
Results:
Following this structural indication, we synthesized a small set of new molecules endowed with a significant, even if not great, F508del-CFTR rescue activity.
Conclusion:
The cited structural feature seems interesting in the search of new correctors. To corroborate this observation, later on we found a new pyrazine derivative (Novartis) endowed with a potent activity as corrector and having the cited common design.
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