This technology includes small molecule inhibitors of O-linked N-acetyl glucosamine (OGlcNAc) transferase (OGT) as molecular probes to better understand OGT function in cell homeostasis, and to eventually be used as therapeutic agents against cancer and to reduce viral replication. OGT is a ubiquitous enzyme catalyzing the transfer of N-acetylglucosamine to the serine or threonine residues of nuclear and cytoplasmic proteins. This cellular process is tightly regulated and is sensitive to levels of cellular stress and of nutrients levels. In addition, OGT modulation may inform on the metabolic reprograming of cancer cells. The inhibitors developed show on-target OGT engagement, as judged by several readouts but does not appear to alter N- or O-glycan structures substantially.
Inhibitors of OGT could be used alone, or in combination with other agents for the treatment of cancer and to reduce replication of a number of viruses.
The first series of cell-permeable and selective OGT inhibitors with on-target engagement.