Description
E-64 (66701-25-5) is a cell-permeable, epoxysuccinyl peptide irreversible inhibitor of calpain and other cysteine proteases.1,2?Inhibits calpain-dependent apoptosis pathway in T cells3?but promotes heat-induced apoptosis in FM3A cells. Typical working concentration is 0.5-10 μg/ml.4
Uses
It is used as a broad spectrum cysteine proteinase and calpain activation inhibitor. Additionally, Prevotella intermediate studies report that E-64 blocks the breakdown of methaemoglobin and the oxidation of oxyhaemoglobin by InpA. E-64 has also been used to study excystation in Giardia lamblia. E-64 is an inhibitor of Calpain, cathepsin K and cathepsin S. 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
Definition
ChEBI: E64 is an epoxy monocarboxylic acid, a dicarboxylic acid monoamide, a member of guanidines and a L-leucine derivative. It has a role as a protease inhibitor, an antimalarial and an antiparasitic agent. It is a tautomer of an E64 zwitterion.
General Description
E-64 is a cysteine protease inhibitor that was isolated from the mold Aspergillus japonicus TPR-64. E-64 is also known as N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl]-agmatine. E-64 effectively inhibits various cysteine proteases, in particular:
- cathepsin K
- cathepsin L
- cathepsin S
E-64 also acts against other enzymes, such as:
- calpain
- cathepsin B
- cathepsin H
- papain
Hazard
A reproductive hazard.
Biochem/physiol Actions
E-64 is an irreversible, potent, and highly selective cysteine protease inhibitor. E-64 does not react with the functional thiol group of non-protease enzymes, such as L-lactate dehydrogenase or creatine kinase. E-64 will not inhibit serine proteases (except trypsin) like other cysteine protease inhibitors, leupeptin and antipain. The trans-epoxysuccinyl group (active moiety) of E-64 irreversibly binds to an active thiol group in many cysteine proteases, such as papain, actinidase, and cathepsins B, H, and L to form a thioether linkage. E-64 is a very useful cysteine protease inhibitor for use in in vivo studies because it has a specific inhibition, it is permeable in cells and tissues and has low toxicity.
References
1) Wang and Yuen (1994),?Calpain inhibition: an overview of its therapeutic potential; Trends Pharmacol. Sci.,?15?412
2) Barrett?et al.?(1982),?L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H, and L; Biochem. J.,?201?189
3) Sarin?et al.?(1994),?Inhibition of activation-induced programmed cell death and restoration of defective immune responses of HIV+ donors by cysteine protease inhibitors; J. Immunol.,?153?862
4) Zhu?et al.?(1996),?Promotion of heat-induced apoptosis in FM3A cells by protease inhibitors; Biochem. Biophys. Res. Commun.,?225?924
