Ataluren

Ataluren

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Names
IUPAC name 3-[5-(2-Fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid
Other names PTC124
Identifiers
CAS Number	775304-57-9 N
ChEMBL	ChEMBL256997 Y
ChemSpider	9394889 Y
IUPHAR/BPS	7341
Jmol 3D model	Interactive image
KEGG	D09323 Y
PubChem	11219835
UNII	K16AME9I3V Y
InChI InChI=1S/C15H9FN2O3/c16-12-7-2-1-6-11(12)14-17-13(18-21-14)9-4-3-5-10(8-9)15(19)20/h1-8H,(H,19,20) Y Key: OOUGLTULBSNHNF-UHFFFAOYSA-N Y InChI=1/C15H9FN2O3/c16-12-7-2-1-6-11(12)14-17-13(18-21-14)9-4-3-5-10(8-9)15(19)20/h1-8H,(H,19,20) Key: OOUGLTULBSNHNF-UHFFFAOYAJ
SMILES Fc3ccccc3c1nc(no1)c2cc(ccc2)C(=O)O
Properties
Chemical formula	C15H9FN2O3
Molar mass	284.24 g/mol
Vapor pressure	{{{value}}}
Pharmacology
ATC code	M09AX03
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Ataluren, formerly known as PTC124, is a pharmaceutical drug for the treatment of Duchenne muscular dystrophy and potentially other genetic disorders. It was designed by PTC Therapeutics and is sold under the trade name Translarna in the European Union.

Medical uses

Ataluren has been tested on healthy humans and humans carrying genetic disorders caused by nonsense mutations, such as some people with cystic fibrosis and Duchenne muscular dystrophy. It is approved for the use in Duchenne in the European Union.

Mechanism of action

Ataluren makes ribosomes less sensitive to premature stop codons (referred to as "read-through"). This may be beneficial in diseases such as Duchenne muscular dystrophy where the mRNA contains a mutation causing premature stop codons or nonsense codons. There is ongoing debate over whether Ataluren is truly a functional drug (inducing codon read-through), or if it is nonfunctional, and the result was a false-positive hit from a biochemical screen based on luciferase.

In cystic fibrosis, early studies of ataluren show that it improves nasal potential difference. Ataluren appears to be most effective for the stop codon 'UGA'.

History

Clinical trials

In 2010, PTC Therapeutics released preliminary results of its phase 2b clinical trial for Duchenne muscular dystrophy, with participants not showing a significant improvement in the six minute walk distance after the 48 weeks of the trial. This failure resulted in the termination of a $100 million deal with Genzyme to pursue the drug.

Phase 2 clinical trials were successful for cystic fibrosis in Israel, France and Belgium. Multicountry phase 3 clinical trials are currently in progress for cystic fibrosis in Europe and the USA.

Approval

On 23 May 2014 ataluren received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). Translarna was first available in Germany, the first EU country to launch the new medicine.

In August 2014, ataluren received market authorization from the European Commission to treat patients with nonsense mutation Duchenne muscular dystrophy. A confirmatory phase III clinical trial is ongoing. The drug does not yet have approval by the US Food and Drug Administration.

See also

• Biostrophin and rimeporide, other drugs against Duchenne muscular dystrophy
• Ivacaftor and lumacaftor, other drugs against cystic fibrosis in development by Vertex Pharmaceuticals

External links

• Ataluren's official page on PTC Therapeutics's website

• http://www.marketwatch.com/story/ptc-therapeutics-receives-positive-opinion-from-chmp-for-translarna-ataluren-2014-05-23