BI-1230 is a potent and digit nanomolar inhibitor of HCV NS3 protease and of viral replication. BI-1230 is also highly selective against other serine/cysteine proteases. It also shows good Pharmacokinetic(PK) activity.
HCV NS3 protease is a 180-amino acid chymotrypsin-like serine protease. Its function is the auto-proteolytic cleavage of HCV viral polyprotein into individual, non-structural (NS) proteins with various functions. Thus it is an essential component of HCV replication and infectivity. The NS3 protein contains two functional domains: a serine protease- and a helicase domain. The active site of NS3 is located in the shallow and wide protein-protein interaction surface of these domains. BI-1230 and other known NS3 inhibitors cover significant parts of this interaction surface in addition to the active site.
BI-1230 binds to the active site of NS3 that is located in the shallow and broad protein-protein interaction surface of the protease and the helicase domain of the enzyme. It is a single-digit nanomolar inhibitor of protease activity and of viral replication that was shown to be highly selective against other serine/cysteine proteases. The pharmacokinetic evaluation shows good half-life and bioavailability, making BI-1230 a valuable in vitro and in vivo tool compound.
Additionally, BI-1230 (60 min incubation) exhibits an IC50 value of 6.7 nM in an Enzymatic assay. BI-1230 (72 hours) shows EC50 values of 4.6 nM and <1.8 nM in a Cell-based HCVPV RNA replication Luciferase reporter assay, genotype background 1a and 1b, in Huh7 cells.
BI-1230 exhibits F% potency of 42%, 92% and 45% in rat, dog and monkey, respectively.