Our project, aiming to the development of new correctors for the rescue of mutant CFTR, is based on a close collaboration between the medicinal chemist group of the University of Palermo and  the research group of TIGEM di Pozzuoli. 

We have identified a class of new small molecules with high efficacy as F508del-CFTR correctors particularly in combination with class 1 correctors such as VX-809. Development of new CFTR modulators may be beneficial for the treatment of patients with F508del and other CF-causing mutations. Starting from a first candidate, we have progressively improved the efficacy and potency by iterative cycles of chemical synthesis followed by functional testing of compounds as correctors on CFBE41o- cells expressing F508del-CFTR and validation on primary airway epithelial cells  experiments. Several compounds appear promising for the future development of combinatorial treatments for CF. Our main objective was to obtain a lead compound endowed with high activity and acceptable drug-like properties. 

We have also achieved a new family of active compounds by chemical manipulation of the parent scaffold. This result is particularly interesting as we will be able to expand our studies (Molecole 3.0 FFC Ricerca project) to both classes of compounds in order to maximize our chances to generate a candidate for preclinical and clinical development, particularly suited for combinatorial treatments to treat patients with F508del and other CF-causing mutations.