8-hydroxyquinoline based small molecule inhibitors of the endoprotease Ras converting enzyme

Abstract

Ras converting enzyme (Rce1p) has been the focus of research due to the prevalence of Ras mutants in cancerous tissues. In vivo studies have shown inactivation of Rce1p causes the mislocalization of Ras; therefore inhibition of Rce1p might have applications in cancer treatment. Several inhibitors of Rce1p have been identified, including 4-((8-hydroxyquinolin-7-yl)(phenyl)methylamino)benzoic acid. The 8-hydroxyquinoline motif found in this molecule has been used extensively for its metal binding properties. The mechanism of Rce1p has been the subject of some debate, although, it is likely a zinc metalloprotease. Described here are several analogous molecules that display stronger Rce1p inhibition and looser zinc binding.