BMS-790052

BMS-790052 is a first-in-class, nonstructural protein 5A (NS5A) replication complex inhibitor with an EC50 of 9-50 pM. It is one of the most potent inhibitors of HCV replication reported so far. BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with EC50 of 7–13 pM. Residue 30 of NS5A is an important site for BMS-790052-mediated resistance in the hybrid replicons. BMS-790052 was well tolerated in all dose groups, with adverse events occurring with a similar frequency in BMS-790052- and placebo-treated groups. BMS-7590052 is the first NS5A replication complex inhibitor with multiple dose proof-of-concept in clinic. At doses of 1-100 mg daily, BMS-790052 was well tolerated, had a PK profile supportive of once-daily dosing, and produced a rapid and substantial decrease in HCV-RNA levels in patients chronically infected with HCV genotype 1.