Small-molecule inhibitor: SCH6

Name

History: SCH6 was amongst compounds described by J. Edwin et al. in International Patent Application WO02/08244 (2002). Its effect in suppressing one of the biological effects of the hepatitis C virus was described by Foy et al. (2003).
Peptidases inhibited: SCH6 is known only as an inhibitor of hepacivirin.
Mechanism: Inhibition is competitive. K_i is 7 nM for the wild-type peptidase, but higher for some mutated forms that can evolve in vivo under selection by the inhibitor (Yi et al., 2005).
Pharmaceutical relevance: Hepacivirin is essential for the replication of the hepatitis C virus and also contributes to immune evasion by the virus (Foy et al., 2003; Li et al., 2005). Accordingly, the peptidase is an important drug target, and SCH6 is under consideration for therapeutic use.

Inhibitor class: This compound is one of the series of ketoamide inhibitors of hepacivirin. An early report of the effectiveness of the ketoamide warhead in hepacivirin inhibitors was that of Han et al. (2000). A representation of the structures of the compounds BILN-2061, VX-950, SCH 503034 and SCH6 (Yi et al., 2005) shows that they contain a common structural core (high-lighted in blue above) that corresponds to parts of the P2 and P1 residues of a peptide substrate.