New Quinolinone O-GlcNAc Transferase Inhibitors Based on Fragment Growth.

ABSTRACT: O-GlcNAcylation is an important post-translational and metabolic process in cells that must be carefully regulated. O-GlcNAc transferase (OGT) is ubiquitously present in cells and is the only enzyme that catalyzes the transfer of O-GlcNAc to proteins. OGT is a promising target in various pathologies such as cancer, immune system diseases, or nervous impairment. In our previous work we identified the 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives as promising compounds by a fragment-based drug design approach. Herein, we report the extension of this first series with several new fragments. As the most potent fragment, we identified 3b with an IC₅₀ value of 116.0 μM. If compared with the most potent inhibitor of the first series, F20 (IC₅₀ = 117.6 μM

SUBMITTER: Weiss M 

PROVIDER: S-EPMC8079942 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature