ataluren

Ligand id: 7341

Name: ataluren

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 76.22
Molecular weight 284.06
XLogP 4.49
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
This drug was granted orphan designation by the European Medicines Agency (EMA) in 2005. Since then, clinical trials have been further assessing the efficacy of this drug in patients with nonsense mutation dystrophinopathy. Preliminary results from clinical trials testing ataluren are now being reported [2] and more trials are underway. Click here to view current clinical trials of ataluren/PTC124 registered at ClinicalTrials.gov. Trial NCT02090959 is a confirmatory Phase III extension study in 220 patients with nonsense mutation dystrophinopathy which is a 96 week trial due for completion in mid-June 2014. On 22 May 2014 the EMA adopted a positive opinion, recommending the granting of a conditional marketing authorisation for ataluren (view the Committee for Medicinal Products for Human Use (CHMP) opinion).
Ataluren is also being investigated for use in patients with nonsense mutation cystic fibrosis in Phase III studies (NCT00803205 and NCT01140451). A Phase IIa study in patients with nonsense mutation hemophilia A and B (NCT00947193) has been suspended.
Mechanism Of Action and Pharmacodynamic Effects
Studies have shown that the mechanism of action involves suppression of ribosome-induced termination of protein translation at premature termination codons (PTCs) whilst still recognising genuine stop codons [4]. By increasing the ability of the ribosome to ignore PTCs, increased amounts of functional full-length proteins are produced. However, the validity of the claimed action of this chemical has been questioned [3].
In Duchenne muscular dystrophy (DMD) the dystrophin gene carries a PTC in around 10 to 15% of patients.