Small-molecule inhibitor: E64d

Name

History: This compound, the ethyl ester of Ep475 was described by Tamai et al. (1986).
Peptidases inhibited: Presumably similar to Ep-475.
Mechanism: Presumably similar to that of Ep-475.
Pharmaceutical relevance: Inhibited neurite outgrowth and induced liver injury in rats (Song et al., 1994; Fukushima et al., 1990).

CID at PubChem: 65663
ChEBI: 199106
Structure
Chemical/biochemical name: ethyl 3-[[3-methyl-1-(3-methylbutylcarbamoyl)butyl]carbamoyl]oxirane-2-carboxylate; ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbomoyl]-2-oxiranecarboxylate
Formula weight: 342

Inhibitor class: This compound is of the epoxysuccinate class of inhibitors, which affect primarily cysteine peptidases in clan CA. The compounds inhibit irreversibly by S-alkylation of the catalytic cysteine, which results in opening of the epoxide ring. A thioester bond is formed by nucleophilic attack at C2 or C3 of the epoxide ring. Powers et al. (2002) (pp. 4664-4675) provide an authoritative review of epoxysuccinyl peptides as peptidase inhibitors.
Comment: This is a more membrane-permeant proinhibitor of Ep475, which is presumably converted to Ep475 by esterase activity once inside the cell.