Small-molecule inhibitor: lisinopril

Name

History: Lisinopril is a lysine analogue of enalapril (MK-421) described by Brunner et al. (1981) and initially termed MK-521 (Ulm et al., 1982).
Peptidases inhibited: Angiotensin-converting enzyme compound peptidase (K_i = 0.1 nM: Bull et al., 1985). Both peptidase units of the compound peptidase (M02.001, M02.004) are inhibited with similar though not identical potency (Wei et al., 1992).
Mechanism: Inhibition is reversible. The structure of a complex between human testicular ACE and lisinopril has been described (Natesh et al., 2003).
Pharmaceutical relevance: Lisinopril is one of the orally-active inhibitors of angiotensin-converting enzyme compound peptidase that are used as drugs to control hypertension.
DrugBank: DB00722

CID at PubChem: 5362119
ChEBI: 43755
Structure
Chemical/biochemical name: N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; (2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenyl-propyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid
Formula weight: 405
Related inhibitors: A derivative selective for angiotensin-converting enzyme domain 2 has been termed lisW-S, and the crystal structure of the complex determined (Watermeyer et al., 2010).

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).
Comment: Immobilised lisinopril can be used for the affinity purification of angiotensin-converting enzyme (Bull et al., 1985).