This project is also part of the FFC-enabled program aimed at identifying drugs that help develop more effective FC deficiency therapies. There is a belief that treatment with a single corrector is not sufficient to achieve recovery of the clinically relevant F508del defect. A combination of correctors with complementary mechanisms is instead desirable to maximize the recovery of the mutated protein. To this end, the project intends to try its hand, starting from the study of 200 compounds previously synthesized, from which emerged a lead compound, subsequently improved, with the confirmation of its mechanism of action and functional recovery of the F508del-CFTR protein. The project aims to synthesize new derivatives that are endowed with maximum efficacy and affinity for the mutated CFTR protein. New classes of tricyclic compounds are involved, which will be tested on CF cell lines and primary CF epithelial cells (bronchial and/or nasal) to verify their activity. Biochemical and microscopy assays are also planned to evaluate the effect on maturation and transport of the F508del-CFTR protein. It is planned to generate a new class of small molecules for the correction of the CF basic defect, with particular ability to perform a synergistic action with the first-generation correctors already known.