Small-molecule inhibitor: telaprevir

Name

History: The development of VX-950 has been described by Chen & Tan (2005).
Peptidases inhibited: VX-950 inhibits hepacivirin with K_i values in the order of 40 nM that do not vary greatly between the peptidases from subtypes 1, 2 and 3 of the virus (Lin et al., 2005; Tong et al., 2006. The compound is regarded as a highly selective inhibitor of hepacivirin.
Mechanism: Inhibition is reversible.
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 VX-950 has been considered for therapeutic use, and has been subjected to Phase I clinical trials.

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.
Reviews: Tong et al. (2006)