Abstract
Methionine aminopeptidases (MetAPs) have been investigated for decades, and pharmacological inhibition of MetAPs has been pursued to treat diseases such as viral infection, cancer, obesity and inflammatory diseases. This review summarizes the current knowledge of this evolutionary conserved enzyme class, which consists of two main subtypes, MetAP1 and MetAP2. The main focus is on summarizing the literature of the past decade, since comprehensive reviews were published. Herein, we consider cofactors and structural features, as well as classes of pan- and subtype-selective inhibitors. Physiology and pathophysiology are reviewed and a comprehensive overview of clinical studies is summarized, focusing on MetAP2 inhibitors. Up to date irreversible MetAP2 inhibitors failed in clinic trials due to either lack of efficacy, unfavorable PK properties or side-effects. The noncovalent, reversible drug M8891 is the first reversible MetAP2-selective inhibitor and has been recently progressed into clinical Phase I development.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
