In this project, a continuation of FFC#4/2020, the research group wants to deepen the knowledge on the interaction mechanisms between the ARN23765 corrector, obtained thanks to the strategic project Task Force for Cystic Fibrosis, and the CFTR channel. Thanks to the previous project, the group has developed a system called Photo-Affinity Labeling (PAL) capable of showing, within living cells, the interaction between ARN23765 and the CFTR channel both mutated (F508del) and not. The results of FFC#4/2020 showed for the first time the interaction between a corrector and its target (mutated CFTR) in an intact cellular environment. In this project, still using the PAL approach, the research group wants to identify at the molecular level the binding site between CFTR and ARN23765 to discover the correction mechanism. Computational and functional studies will be performed to identify the protein regions of CFTR involved in the correction of ARN23765. The identification of the mechanism of action of ARN23765 will help strengthen its profile as a candidate for preclinical development for the treatment of cystic fibrosis. Moreover, thanks to this study, the PAL strategy could represent a complementary procedure to study the mechanism of action of CFTR modulators.