Optimization of a new lead promoting the readthrough of nonsense mutations for the CFTR rescue in human CF cells

Progetto: Research project

Dettagli progetto


Cystic Fibrosis (CF) patients with nonsense (ns) mutations in the CFTR gene have a more severe form of the disease. A potential treatment is to promote translational readthrough of premature termination codons (PTCs) by Translational Read-Through-Inducing Drugs (TRIDs). By computational and biological screening we identified, a new small molecule (NVX) showing high readthrough activity. Our intent is to evaluate the CFTR functionality after NVX treatment in CF model systems and the activity of new lead molecules, in cells expressing a nonsense-CFTR-mRNA (ns CFTR). Finally, we will study the supramolecular interactions among TRIDs, CFTR mRNA and ribosomal A-site to assess the biological target/mechanism.

Layman's description

QSAR study of our new LEAD molecule Synthesis and Characterization of a small library of compounds as suggested by the computational study.Analysis of the CFTR functionality Induced Fit docking and Molecular dynamics Study of molecule safety profile

Key findings

Data di inizio/fine effettiva9/1/179/1/17