Endothelin converting enzyme (ECE) from intact cells of a permanent human endothelial cell line, EA.hy926, was studied by examining the effects of phosphoramidon, an endothelin converting enzyme inhibitor, on the levels of secreted endothelin‐1 and big endothelin‐1. The specific ECE activity was demonstrated by a phosphoramidon dose‐dependent decrease in ET‐1 level with a concomitant increase in big ET‐1 level. By using a specific neutral endopeptidase 24.11 (NEP 24.11) inhibitor, thiorphan, it was also shown that the phosphoramidon‐sensitive ET‐1 degrading activity in this cell line is due to the NEP 24.11 activity. Other serine, acid, and cysteine protease inhibitors had no effect on the endogenous synthesis of ET‐1 and big ET‐1 supporting the evidence that ECE is insensitive to these protease inhibitors as has been demonstrated with the isolated enzyme.
Synthesis of Novel Substituted Pyridines as Inhibitors of EndothelinConverting Enzyme-1 (ECE-1).-A series of heteroaryl substituted pyridine carboxylic acids is prepared and evaluated as inhibitors of ECE-1. These compounds are prepared by Pd-catalyzed cross couplings of halogenated pyridines with heteroaryl organometallics. The thiazole-4-yl moiety is found to be the most active one. -(MASSA, M. A.; PATT, W. C.; AHN, K.; SISNEROS, A. M.; HERMAN, S. B.; DOHERTY, A.; Bioorg. Med. Chem.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.