Caspases are enzymes belonging to the cysteine protease family, consisting of 12 family members, that play a critical role in apoptosis. Inhibition of caspase activity is potentially beneficial in degenerative disorders such as Alzheimer's disease (AD), Parkinson's, and Huntington's diseases. A tetrapeptide containing the sequence Ile-Glu-Thr-Asp and an aldehyde warhead covalently bonded to Cys360 in the active site of caspase-8. Acetic acid derivatives inhibiting caspase-3 with micromolar IC50 values have been identified. Caspase inhibitors are well known in the literature. However, a group of thiol-containing compounds have been recently identified to inhibit caspase activities. Instead of targeting the active site cysteine residue, these compounds, known as "disulfide tethers", bind to an allosteric site and trapping the enzyme in an inactivated (zymogen) state. FICA and DICA, indole and dichlorophenoxy derivatives, respectively, are examples of "sulfur tethers" which binds at the dimeric interface of caspase-7 to form a disulfide linkage with Cys290. Two thiol containing thienopyrazoles were found to inactivate caspase-1 267 , and caspase-5, respectively. 268 IDN-6556 (emricasan), a pan caspase oxamyl dipeptide irreversible inhibitor was in phase II clinical trials for treatment of liver diseases. Emricasan in combination with birinapant, a second mitochondria-derived activator of caspases (SMAC) mimetic has shown great therapeutic efficacy and safety in the treatment of AML. 270 A covalent inhibitor of caspase 8 containing an 2-oxoalkyl dichlorobenzoate moiety was designed to form a covalent adduct with Cys360. A similar strategy has also been applied to design covalent inhibitors for caspase 3 and caspase 6. These inhibitors have a 2-oxoalkyl tetrafluorophenyl ether moiety that reacts with a nucleophilic cysteine to release tetrafluorophenol and forming a covalent 2-oxoalkyl cysteinyl ether adduct.