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.