Caspase Inhibitors
During the last decade, the clinical understanding of apoptosis has advanced substantially, not only in experimental models but also in humans. A variety of anti-apoptosis-based therapeutic strategies have been used, but therapeutic approaches that target an individual caspase are now the focus of intense biological and clinical interest. Caspase inhibitors act by binding to the active site of caspases either in a reversible or irreversible manner. Inhibitor design includes a peptide recognition sequence attached to a functional group such as an aldehyde (CHO), chloromethylketone (CMK), or fluoromethylketone (FMK). The peptide recognition sequence corresponding to that found in endogenous substrates determines the specificity of a particular caspase. Cell-permeable, FMK-based caspase inhibitors have played a major role in advancing the anti-apoptosis-based therapeutic research. Recently, Q-XXXX-OPh based cell-permeable, irreversible, second generation caspase inhibitors have also become very popular due to their enhanced potency as well as reduced cellular toxicity. Additionally, these inhibitors also exhibit longer stability than FMKs, making them a better choice for in vivo studies.
