title: CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of cathepsin B within living cells.
abstract: Studies using inhibitors that reportedly discriminate between cathepsin B and related lysosomal cysteine proteinases have implicated the enzyme in a wide range of physiological and pathological processes. The most popular substance to selectively inhibit cathepsin B in vivo is CA-074Me, the methyl ester of the E-64 derivative CA-074. However, we now have found that CA-074Me inactivates both cathepsin B and cathepsin L within murine fibroblasts. In contrast, exposure of these cells to the parental compound CA-074 leads to the selective inhibition of endogenous cathepsin B, while intracellular cathepsin L remains unaffected. These results indicate that CA-074 rather than CA-074Me should be used to specifically inactivate cathepsin B within living cells.
authors.affiliation: Zentrum für Angewandte Genetik, Universität für Bodenkultur Wien, Austria.
authors.forename: Metwally
authors.initials: M
authors.lastname: Montaser
authors.forename: Gilles
authors.initials: G
authors.lastname: Lalmanach
authors.forename: Lukas
authors.initials: L
authors.lastname: Mach
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D004151:Dipeptides / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: C400541:CA 074 methyl ester; D004151:Dipeptides; D011480:Protease Inhibitors; C068250:N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534278:Ctsl protein, mouse