Small-molecule inhibitor: enalapril

Name

History: Enalapril was described as an inhibitor of angiotensin-converting enzyme compound peptidase in 1982 (e.g. Millar et al., 1982).
Peptidases inhibited: Angiotensin-converting enzyme compound peptidase. The two peptidase units (M02.001, M02.004) are inhibited with approximately similar, nanomolar potency (Bevilacqua et al., 1996).
Mechanism: Enalaprilat (often as its maleate, MK-421) is an ethyl ester pro-inhibitor of the active diacid (enalapril, MK-422) (Sweet, 1983). N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro inhibited angiotensin-converting enzyme with a K_i of 0.05 nM (Shapiro & Riordan, 1984).
Pharmaceutical relevance: Enalapril is in clinical use as a treatment for hypertension (Kostis et al., 2004).
DrugBank: DB00584

CID at PubChem: 53370
ChEBI: 330122
Structure
Chemical/biochemical name: N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro, or 1-[2-(1-ethoxycarbonyl-3-phenyl-propyl)aminopropanoyl]pyrrolidine-2-carboxylic acid
Formula weight: 376
Related inhibitors: 1-[2-(1->ethoxycarbonyl-3-phenyl-propyl)aminopropanoyl]pyrrolidine-2-carboxylic acid; N-[(S)-1->carboxy-3-phenylpropyl]-L-Ala-L-Pro

Inhibitor class: This is a compound in the carboxylate class of reversible metallopeptidase inhibitors. In these, the active site zinc of the enzyme is generally coordinated by a carboxylate of the inhibitor, and this interaction contributes to inhibitory potency. Reviewed by Patchett & Cordes (1985) and Powers & Harper (1986), pp. 268 - 277 (who provide a table of K_i values).