Small-molecule inhibitor: boceprevir

Name

History: SCH 503034 was fully described in 2006 (Malcolm et al., 2006; Tong et al., 2006) after the synthesis had been reported in 2005 (Njoroge et al., Abstr. 230th Am. Chem. Soc. Natl. Meet., abstr 252, 2005).
Peptidases inhibited: SCH 503034 is known only as an inhibitor of hepacivirin. The overall inhibition constant is 14 nM (Malcolm et al., 2006).
Mechanism: Inhibition is competitive.
Pharmaceutical relevance: Hepacivirin is essential for the replication of the hepatitis C virus and also contributes to immune evasion by the virus (Li et al., 2005). Accordingly, the peptidase is an important drug target, and SCH 503034 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.