PD 069185 is a highly selective and structurally novel inhibitor of endothelin converting enzyme-1 (ECE-1). PD 069185 is a trisubstituted quinazoline and has an IC50 value of 0.9 /iM for human ECE-1 inhibition. Kinetic analysis revealed that PD 069185 is a competitive inhibitor with a Ki value of 1.1 /iM and act in a reversible fast-binding manner. The closely related enzyme, ECE2, is not inhibited at up to 100 M PD 069185. In addition, PD 069185 at 100 fiM has no effect on other metalloproteases, such as neutral endopeptidase 24.11 and stromelysin, showing a high ECE-1 specificity. Selected analogs in this series will be profiled. This non-peptide ECE-1 inhibitor should serve as a valuable tool to study the pathophysiological role of endothelin and the therapeutic potential of ECE-1 inhibitors.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology