Therapeutic potential of endothelin converting enzyme inhibitors

Endothelin-1 (ET-1) is a potent peptidic vasoconstrictor. Similar to many other peptidic hormones, ET-1 is initially synthesised as a large precursor and subsequently cleaved by proteolytic enzymes to form the mature peptide. The final step of post-translational processing is catalysed by endothelin converting enzyme (ECE). Thus, inhibitors of ECE should suppress the biosynthesis of ET-1 and, therefore, would have beneficial effects on diseases where an overproduction of ET-1 may play a pathogenic role. This article reviews the in vitro and in vivo activities of patented ECE inhibitors. The effects of ECE inhibitors on various animal models of cardiovascular, renal, and central nervous system disorders are summarised.