Safety and Antiviral Activity of MK-5172, a Novel HCV NS3/4a Protease Inhibitor with Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients

• MK-5172 is a novel, competitive inhibitor of the HCV NS3/4a protease with selective, potent in vitro activity against a broad range of HCV genotypes (GTs) and known viral variants that are resistant to other protease inhibitors in development. • MK-5172 exhibits excellent selectivity over other serine proteases such as elastase and trypsin (no measurable inhibition), and shows only modest inhibitory potency with chymotrypsin (IC 50 = 1.5 μM; 75,000-fold selective). • In the genotype 1b replicon assay, MK-5172 potently inhibits viral replication (IC 50 = 2 nM) and demonstrates a modest shift in the presence of 50% NHS (EC 50 = 9.5 nM). In vitro, MK-5172 inhibits the NS3/4A enzyme from genotypes 1b, 2a, 2b, and 3a with K i values of <0.02, 0.15, 0.02, and 0.7 nM, respectively. The genotype 2a replicon is also potently inhibited by MK-5172 (EC 50 = 5 nM).