Ataluren

Pharmaceuticals -> Musculo-skeletal system -> Other drugs for disorders of the musculo-skeletal system

Pharmaceuticals -> Listed in ZINC15

This chemical does not meet GHS hazard criteria for 100% (2 of 2) of all reports.

Not Classified

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

M - Musculo-skeletal system

QM - Musculo-skeletal system

Ataluren enables ribosomal readthrough of mRNA containing premature stop codons that otherwise would result in premature termination of protein chains. Use of ataluren allows cellular machinery to bypass nonsense mutations in genetic material, continue the translation process, and thereby restore the production of a full-length, functional protein. The research on the effects of Ataluren on the translation and stability of nonsense-containing mRNA in vitor show that Ataluren promoted readthrough at each of the nonsense codons, showing maximal activity with UGA, while having no effect on mRNA levels. Unlike the stable cell line assays, Ataluren did not discriminate significantly between the UAG and UAA mRNAs. Ataluren was a more potent nonsense-suppressing agent than gentamicin, and exhibited 4- to 15-fold stimulation of in vitro readthrough relative to the controls at levels similar to those in the stable cell reporter assays. These results indicate that Ataluren modulates termination efficiency at premature nonsense codons.

Ataluren is metabolized by conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, predominantly UGT1A9 in liver and intestine. In vivo, the only metabolite detected in plasma after oral administration of radio-labelled ataluren was the ataluren-O-1β-acyl glucuronide; exposure to this metabolite in humans was approximately 8% of the plasma AUC of ataluren.

Peak plasma levels of ataluren are attained approximately 1.5 hours after dosing in subjects who received medicinal product within 30 minutes of a meal.

After a single oral dose of radiolabeled ataluren, approximately half of the administered radioactive dose is recovered in the faeces and the remainder was recovered in the urine. In the urine, unchanged ataluren and the acyl glucuronide metabolite account for less than 1% and 49%, respectively, of the administered dose.