Small-molecule inhibitor: captopril (XM02.001)

Name

Common name: captopril (XM02.001)
Other names: D-2-methyl-3-mercaptopropanoyl-L-Pro; silicaptopril; SQ14225; SQ 14225

History: Captopril (as SQ14225) was the most potent of a series of inhibitors of angiotensin-converting enzyme compound peptidase described by Cushman et al. (1977).
Peptidases inhibited: Shows considerable specificity for the angiotensin-converting enzyme compound peptidase, affinity being highest for peptidase unit 1, but unit 2 also being inhibited (Bevilacqua et al., 1996). Much more weakly, inhibits meprin A complex peptidase: Kruse et al., 2003), leukotriene A4 hydrolase: Orning et al., 1991) and peptidyl-dipeptidase Dcp: Deutch & Soffer, 1978). Crystal structures have been described for complexes with angiotensin-converting enzyme (Kim et al., 2003; Natesh et al., 2004) and leukotriene A4 hydrolase (Thunnissen et al., 2002). Does not inhibit angiotensin-converting enzyme 2: Tipnis et al., 2000) or endothelin-converting enzyme-1.
Mechanism: Inhibition is reversible.
Pharmaceutical relevance: Captopril is used as a drug for the control of blood pressure by inhibition of angiotensin-converting enzyme.
DrugBank: DB01197

Inhibitor class: This compound is a thiol-containing metallopeptidase inhibitor. In these, an interaction between the thiol group of the inhibitor and zinc in the active site of the enzyme contributes to inhibitory potency. Among the first of such compounds to be described was captopril (Cushman et al., 1977). Reviewed by Powers & Harper (1986), pp. 254 - 263. Thiol-containing metallopeptidase inhibitors include captopril, CGS 35601, GEMSA, omapatrilat, RB 101(S), thiorphan.