Loxistatin acid [E-64c]

E-64c is a potent cell-impermeable epoxysuccinyl peptide inhibitor of calpain and other cysteine proteases, such as papain, cathepsin B, H and L. Does not inhibit the serine proteases trypsin, chymotrypsin or elastase. E-64c is an active metabolite of the protease inhibitor E-64d (Prod. No. AG-CR1-3737), and a synthetic analog of E-64 (Prod. No. AG-CP3-7006). Studies indicate that E-64c is a more potent inhibitor of cathepsins B and L compared to E-64. E-64c has in vitro antiviral, antiparasitic and immunomodulatory properties. It reduces the autocatalytic activity of the foot-and-mouth-disease virus (FMDV) leader protease, reduces infection of HEK293T cells by an HIV-based virus system pseudotyped with SARS-CoV spike glycoprotein in a concentration-dependent manner, inhibits human rotavirus replication, and exhibits entry-blocking effects against MERS-CoV. It also inhibits the trypanosomal cysteine protease cruzain. Significantly reduces calpain-mediated depletion of microtubule-associated protein (MAP2) in an animal model of an ischemic brain.