Pharmacological inhibitors of the nonsense-mediated RNA decay identified by high-throughput screening. (PubMed, RNA) - Sep 23, 2026 - "CF patients carrying a nonsense mutation in the CFTR gene are insensitive to CFTR modulators and cannot benefit from the pharmacological therapy with Kaftrio®...At the end of the screening, we identified and validated by secondary assays three possible candidates acting as NMD inhibitors/modulators that could increase CFTR rescue in patients with PTCs, namely CC-115, samotolisib and elimusertib. The study also provides new insights into the changes occurring to cells transcriptome after the inhibition of the physiological NMD pathway, improving our knowledge of possible side effects of NMD inhibitors. This could help in the development of new compounds with more efficacy and less toxicity, that could be useful for the treatment of different genetic disorders caused by PTCs."
Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR
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Anna Borrelli; Arianna Venturini; Luis J V Galietta; Martina De Santis; Nicolina Cristina Sorrentino; Rossella De Cegli
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