O-linked N-acetylglucosamine transferase (OGT)

O-linked N-acetylglucosamine transferase (OGT) is a vital enzyme that catalyzes the addition of a single N-acetylglucosamine sugar to the serine and threonine residues of intracellular proteins, a process known as O-GlcNAcylation [1][2]. As the only enzyme capable of performing this modification, OGT serves as a key nutrient sensor, integrating cellular metabolic status with signaling pathways and gene expression [2][3]. It regulates a vast array of substrates, including transcription factors, cytoskeletal proteins, and signaling kinases, influencing processes such as the cell cycle, apoptosis, and the stress response [1][4]. Aberrant OGT activity and elevated O-GlcNAc levels are frequently observed in various cancers, where they drive proliferation, survival, and metastasis [5]. Furthermore, OGT is implicated in the pathogenesis of insulin resistance in type 2 diabetes and the formation of neurofibrillary tangles in Alzheimer's disease [3][6]. While no OGT inhibitors are currently FDA-approved, several small-molecule inhibitors like OSMI-1 and OSMI-4 are extensively used in research to explore the therapeutic potential of targeting this enzyme in oncology and metabolic diseases [7]. The development of potent and selective OGT inhibitors remains a high priority for treating diseases characterized by hyper-O-GlcNAcylation.

Other names

UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferaseO-GlcNAc transferaseHRNT1OGT1

Inhibition of O-GlcNAc transferase activity to prevent the addition of O-GlcNAc moieties to substrate proteins, thereby modulating downstream signaling and metabolic pathways.