PTC-124

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.¹ 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.² 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.³ 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.^1,3,4,5

WARNING This product is not for human or veterinary use.

1. Finkel, R.S. Read-through strategies for suppression of nonsense mutations in Duchenne/Becker muscular dystrophy: Aminoglycosides and ataluren (PTC124). J. Child Neurol. 25(9), 1158-1164 (2010).

2. Du, M., Liu, X., Welch, E.M., et al. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc. Natl. Acad. Sci. USA 105(6), 2064-2069 (2008).

3. Auld, D.S., Thorne, N., Maguire, W.F., et al. Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression. Proc. Natl. Acad. Sci. USA 106(9), 3585-3590 (2009).

4. Wilschanski, M., Miller, L.L., Shoseyov, D., et al. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. Eur. Respir .J. 38(1), 59-69 (2011).

5. McElroy, S.P., Nomura, T., Torrie, L.S., et al. A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. PLoS Biol. 11(6), 1-8 (2013).