Therapeutic potential of glutaminyl cyclases: Current status and emerging trends

Abstract

Glutaminyl cyclase (QC) activity has been identified as a key effector in distinct biological processes. Human glutaminyl-peptide cyclotransferase (QPCT) and glutaminyl-peptide cyclotransferase-like (QPCTL) are considered attractive therapeutic targets in many human disorders, such as neurodegenerative diseases, and a range of inflammatory conditions, as well as for cancer immunotherapy, because of their capacity to modulate cancer immune checkpoint proteins. In this review, we explore the biological functions and structures of QPCT/L enzymes and highlight their therapeutic relevance. We also summarize recent developments in the discovery of small-molecule inhibitors targeting these enzymes, including an overview of preclinical and clinical studies.

Keywords: Alzheimer’s disease (AD); cancer; drug discovery and development; glutaminyl cyclase (QC); glutaminyl-peptide cyclotransferase (QPCT); glutaminyl-peptide cyclotransferase-like (QPCTL); inflammation; pyroglutamate residue (pE); small-molecule inhibitors.