Novel epoxysuccinyl peptides. A selective inhibitor of cathepsin B, in vivo.
New derivatives of E-64 (compound CA-030 and CA-074) were tested in vitro and in vivo for selective inhibition of cathepsin B. They exhibited 10,000-30,000 times greater inhibitory effects on purified rat cathepsin B than on cathepsin H and L: their initial Ki values for cathepsin B were about 2-5 nM, like that of E-64-c, whereas their initial Ki values for cathepsins H and L were about 40 200 microM. In in vivo conditions, such as intraperitoneal injection of compound CA-030 or CA-074 into rats, compound CA-074 is an especially potent selective inhibitor of cathepsin B, whereas compound CA-030 does not show selectivity for cathepsin B, although both compounds CA-030 and CA-074 show complete selectivity for cathepsin B in vitro.
Towatari
T
T
Division of Enzyme Chemistry, University of Tokushima, Japan.
Nikawa
T
T
Murata
M
M
Yokoo
C
C
Tamai
M
M
Hanada
K
K
Katunuma
N
N
D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases; D004151:Dipeptides / Q000494:pharmacology*; D010450:Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004151:Dipeptides; C068249:N-(3-ethoxycarbonyloxirane-2-carbonyl)-isoleucyl-proline; C068250:N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D056655:Cathepsin H; C534128:Ctsh protein, rat; D007930:Leucine; C024974:E 64