Background. Cystic Fibrosis patients with nonsense-mutation in the CFTR gene generally make virtually no CFTR protein and thus often have a more severe form of CF. Recently, Ataluren (formerly PTC124) was suggested to induce the read-through of premature termination codons (PTCs) mainly the UGA codon. However, despite promising results there is not a general consensus of Ataluren efficacy and mechanism of action.

Hypothesis and objectives. The design of new small molecules (PTC124 related) together with the understanding of their mechanism of action could lead to new pharmacologic approaches for the cure of CF caused by nonsense mutations in the CFTR gene. This project was aimed to evaluate the activity of some PTC124 analogues identified by a virtual screening, by different orthogonal assays with vectors containing PTCs in reporter genes and in CF bronchial epithelial cells.