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E-64 is an Irreversible, potent and highly selective inhibitor of cysteine proteases. Does not affect cysteine residues in other enzymes. Acts by forming a thioether bond with thiol of the active cysteine. E-64 will not inhibit serine proteases (except trypsin), but inhibits activation-induced programmed cell death and restores defective immune responses in HIV. Specific active site titrant.

E-64 inhibits calpain, papain, and cathepsin B, cathepsin L. The compound has been reported to inhibit intracellular Bax protease activity, and reduce oxidative stress, which includes a decrease in MDA levels, ICAM-1 expression and MOP activity. E-64 has also been used to study excystation in Giardia lamblia.

E-64 reduces inflammation in cystic fibrosis patients. E-64 plays a role in stabilizing the cytoskeleton protein Synaptopodin (Synpo), as well as, steadying signal transducer and activator of transcription-3 (STAT3). Studies suggest the potential use of STAT3 inhibitors in therapy of glomerular diseases.

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