E-64

The epoxysuccinyl peptide E-64 is an irreversible, potent, and highly selective cysteine protease inhibitor. It inhibits a variety of cysteine proteases, including cathepsins K, L, S, B and H. It inhibits also papain, calpain, ficin and bromelain. Acts by forming a thioether bond with the thiol of the active cysteine. Does not inhibit serine proteases (except reversible inhibition of trypsin) like other cysteine protease inhibitors, e.g. leupeptin and antipain. E-64 is a very useful cysteine protease inhibitor for use for in vitro and in vivo studies because it shows specific inhibition, it is permeable in cells and tissues and has low toxicity. Shown to have diverse biological activities, such as antiviral (FDMV, ASFV), antiparasitic, anticancer and immunomodulatory properties. Shown to reduce bone resorption in embryonic mouse bone explants. Reduces HSC-3 tongue cancer cell invasion and induces oxidative stress and apoptosis in filarial parasites. Inhibits autophagy-associated lysosomal degradation in vitro. E-64 is an effective ligand for affinity purification of cysteine proteases. When coupled to a thiolated affinity matrix, binding is no longer irreversible, but specificity is retained.