Small-molecule inhibitor: omapatrilat

Name

History: Omapatrilat was first described as BMS-186716 by Robl et al. (1997).
Peptidases inhibited: Omapatrilat is a so-called 'vasopeptidase' inhibitor, designed to inhibit both angiotensin-converting enzyme compound peptidase and neprilysin.
Mechanism: Inhibition is reversible.
Pharmaceutical relevance: The inhibition of neprilysin slows the breakdown of atrial natriuretic peptide. Omapatrilat has been subjected to clinical trials in comparison to inhibitors of angiotensin-converting enzyme (Kostis et al., 2004; Solomon et al., 2005).

CID at PubChem: 656629
ChEBI: 288604
Structure
Chemical/biochemical name: 6-oxo-5-(3-phenyl-2-sulfanyl-propanoyl)amino-2-thia-7-azabicyclo[5.4.0]undecane-8-carboxylic acid
Formula weight: 409

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.