Commonly used caspase inhibitors designed based on substrate specificity profiles lack selectivity

Caspase regulation and activation have been extensively studied since the discovery of this class of proteases almost two decades ago, yet surprisingly few tools are available that can be used to monitor individual caspase activities [ 1 ]. The most commonly used tools include caspase-specific anti-sera as well as fluorogenic substrates and inhibitors. Unfortunately, antibody reagents often do not provide an accurate measure of caspase activity since several caspase family members （caspases 8/10 and 9） do not require proteolytic processing for activation [2, 3]. Furthermore, recent evidence suggests that caspase-7 （an executioner caspase） activation occurs via a catalytically active full-length intermediate that cannot be differentiated from the non-cleaved inactive zymogen using antibodies [4, 5].