Ataluren (PTC124)<< Back to CFTR modulators
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Ataluren is a read-through agent designed to overcome premature termination codons (PTCs), or nonsense mutations, in the CFTR gene. In a recent phase III trial, ataluren did not improve lung function and did not decrease pulmonary exacerbations in the overall population of patients with CF and nonsense-mutation who received this treatment, but it might be beneficial for patients not taking chronic inhaled tobramycin.1 Therefore, a further trial is planned of patients not taking nebulised aminoglycosides, which may have been interacting with ataluren.
The mechanism of action is shown below.
Some class I CFTR mutations introduce a premature termination codon (or premature stop codon) into the mRNA sequence.
The stop codon, shown here as UAA, should normally be the last ‘instruction’ in the CFTR gene.
PTCs (highlighted here in red) instruct the process of protein translation to end prematurely.
This produces a truncated (or shortened) version of the CFTR protein, which is subsequently degraded by the cell.
Ataluren binds to ribosomes during the process of translation, forcing ‘read-through’ of the PTC.
The desired effect is that CFTR protein is produced and transported to the cell surface.