Fig 1: Selectivity profile of peptide-based caspase inhibitors.Each caspase was incubated with a saturating concentration of its preferred peptide substrate, in the presence of either the Ac-LESD-CMK, z-LEHD-FMK, z-IETD-FMK, or VX-765 inhibitors at indicated concentrations. Substrate cleavage rates were determined at each inhibitor concentration and normalized to the no inhibitor condition for each run. (A) Chemical structures of Ac-LESD-CMK, z-LEHD-FMK, z-IETD-FMK, and VX-765 inhibitors. (B) Caspase-8 inhibition was assessed using 200 μM Ac-LEHD-AMC substrate. (C) Caspase-10 inhibition was assessed using 200 μM Ac-LEHD-AMC substrate. (D) Caspase-1 inhibition was assessed using 200 μM Ac-WEHD-AMC substrate for activity. (E) Caspase-5 inhibition was assessed using 200 μM Ac-WEHD-AMC substrate. (F) Caspase-3 inhibition was assessed using 100 μM Ac-DEVD-AMC substrate. (G) Caspase-6 inhibition was assessed using 100 μM Ac-DEVD-AMC substrate. (H) Caspase-7 inhibition was assessed using 100 μM Ac-DEVD-AMC substrate. Data were fitted using the [Inhibitor] vs. normalized response function in GraphPad Prism. Data are means ± SEM of three independent experiments.