Asunaprevir

Asunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) NS3 protease inhibitor for the treatment of hepatitis C virus infection. Asunaprevir competitively binds to the NS3/4A protease complex, with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. In cell culture, asunaprevir (BMS-650032) inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Asunaprevir at doses of 200 to 600 mg resulted in rapid HCV RNA decreases from the baseline; maximal mean changes in HCV RNA over time were 2.7 and 3.5 log(10) IU/ml in the SAD and MAD studies, respectively. Plasma and tissue exposures in vivo in several animal species indicated that asunaprevir displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Asunaprevir (BMS-650032) is currently in phase III clinical trials.