PTC-124 (Ataluren) selectively induces ribosomal read-through of premature but not normal termination codons, with EC50 of 0.1 μM, may provide treatment for genetic disorders caused by nonsense mutations (e.g. CF caused by CFTR nonsense mutation).

Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis.PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full-length, functional proteins.In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function.The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC50 = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity.Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.