Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme.

ABSTRACT: Insulin-degrading enzyme (IDE) is a human mononuclear Zn²⁺ -dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation. Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn²⁺ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of ∼350 metal-binding pharmacophores was screened against IDE,

SUBMITTER: Adamek RN 

PROVIDER: S-EPMC8627785 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature