Ataluren, a 1,2,4-Oxadiazole-Containing Drug Candidate for Nonsense Mutations: Major Breakthroughs and an Up-to-Date Process Chemistry Review

Genetic ailments such as Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF) arise due to nonsense mutations. A nonsense mutation occurs when a point mutation changes a sense codon that codes for an amino acid to a stop codon, which leads to premature termination of mRNA translation. Because of this, a truncated protein product is produced; therefore, it is called a premature termination codon (PTC), and several diseases, such as CF, DMD, and congenital myopathy, arise due to the production of a truncated protein. The bioactive compound ataluren, formerly known as PTC124, is believed to modulate the translation machinery and enhance the synthesis of fully functioning, full-length protein by permitting the readthrough of PTCs during mRNA translation. Ataluren, known by the brand name Tranlsarna, is currently authorized to treat nonsense mutations in DMD and other diseases in the European Union and other countries. In this work, an earnest effort has been made to bring about significant breakthroughs and elucidate its mechanisms of action, and an up-to-date synthetic review has been carried out.