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Caspase inhibitors and activators act on cysteine proteases that cleave their substrates after aspartate residues. Initiator caspases such as caspase-8 and caspase-9 activate executioner caspases, including caspase-3, to dismantle the cell during apoptosis. Caspase-1, the first family member, was identified in 1992 as the protease that processes interleukin-1β (IL-1β). Peptide fluoromethyl ketones (FMKs) are the classic inhibitor type, led by the pan-caspase inhibitor Z-VAD-FMK. Z-DEVD-FMK, Z-IETD-FMK and Z-LEHD-FMK prefer caspase-3, caspase-8 and caspase-9, respectively. Q-VD-OPh is a broad caspase inhibitor, and belnacasan inhibits the inflammatory caspases 1 and 4. PAC-1 works in the opposite direction, as a small molecule that activates procaspase-3.
Clofilium tosylate, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3. Antiarrhythmic agent.
