Glecaprevir

Glecaprevir is an orally bioavailable and direct-acting inhibitor of the hepatitis C virus (HCV) non-structural 3/4A (NS3/4A) serine protease.It inhibits NS3/4A from HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a (IC50s = 4.6, 8.9, 3.5, 3.8, 7.9, 6.1, 8.1, and 11.3 nM, respectively) in cell-free assays but does not inhibit human chymase, chymotrypsin type II, chymotrypsin type VII, elastase, kallikrein, urokinase, or cathepsin B proteases (IC50s = >200,000 nM). Glecaprevir inhibits HCV replication in stable Huh7-derived replicon cells infected with subgenomic genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a (EC50s = 0.85, 0.94, 2.2, 4.6, 1.9, 2.8, 1.4, and 0.86 nM, respectively). It also inhibits replication of clinical isolates of genotypes 1a (EC50s = 0.05-0.12 nM), 1b (EC50s = 0.20-0.68 nM), 2a (EC50s = 0.66-1.9 nM), 2b (EC50s = 1.4-3.2 nM), 3a (EC50s =0.71-3.8 nM), and 4a (EC50s = 0.31-0.55 nM). Glecaprevir acts synergistically with the HCV NS5A protease inhibitor pibrentasvir (Item No. 27546) to inhibit HCV genotype 1b-Con1 replication in replicon cells. Formulations containing glecaprevir, in combination with pibrentasvir, have been used in the treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection.