Inside Cover: Induced-Fit Binding of the Macrocyclic Noncovalent Inhibitor TMC435 to its HCV NS3/NS4A Protease Target (Angew. Chem. Int. Ed. 9/2010) (page 1510)
Maxwell D. Cummings, Jimmy Lindberg, Tse-I Lin, Herman de Kock, Oliver Lenz, Elisabet Lilja, Sara Felländer, Vera Baraznenok, Susanne Nyström, Magnus Nilsson, Lotta Vrang, Michael Edlund, Åsa Rosenquist, Bertil Samuelsson, Pierre Raboisson and Kenneth Simmen
Article first published online: 17 FEB 2010 | DOI: 10.1002/anie.201000389
The anti-HCV activity of TMC435, currently in phase 2b clinical studies as an HCV therapeutic (HCV=hepatitis C virus), is based on inhibition of the NS3/4A protease of the virus. As M. D. Cummings and co-workers describe in their Communication on page 1652 ff., binding of TMC435 to the target enzyme involves an induced fit, leading to occupancy of an extended S2 subsite. The authors thank J. M. Berke, E. Fransen, and L. Geeraert for assisting with the graphics.