Narlaprevir

개요Narlaprevir was approved as a treatment for genotype 1 HCV and serves as a class 2 HCV NS3 serine protease inhibitor. In clinical trials, it showed a rapid and steady decline in HCV-RNA levels in both previously treated and treatment-naive patients when used in combination with ritonavir and PEG-IFN-α. This combination ultimately led to ≥50% of patients with undetectable HCV-RNA levels after a second period of treatment. Narlaprevir also has demonstrated activity against HCV mutations resistant to other treatments such as boceprevir and telaprevir. The unique activity of this drug can be attributed to a critical electrophilic α-keto-amide “warhead”, which covalently reacts with an HCV NS3 protease active-site serine residue involved in the HCV viral replication process. Because of their essential roles in viral replication, HCV NS3 and NS5B proteases have recently become key targets for HCV drug development. Strategically, the development of narlaprevir stems specifically from the pursuit of a single-diastereomer, second generation HCV protease inhibitor, which would provide in vitro potency and pharmacokinetic profile improvements over the structurally related antiviral drug boceprevir,which exists as a mixture of diastereomers. After the R-Pharm pharmaceutical group obtained the license to manufacture narlaprevir from Merck in 2012, further development of the drug was realized through collaborations with Schering-Plough and Texas Liver Institute.

용도Narlaprevir is an NS3/4A protease inhibitor used in the treatment of hepatitis C virus, HCV.