OSMI-1

OSMI-1 is a cell-permeable small molecule that serves as a potent and selective inhibitor of **O-GlcNAc transferase (OGT)**. OGT is the enzyme responsible for O-GlcNAcylation, a post-translational modification involving the attachment of N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. By blocking OGT activity, OSMI-1 reduces global protein O-GlcNAcylation levels, which are often elevated in various pathological states including cancer, metabolic disorders, and neurodevelopmental diseases. In preclinical research, OSMI-1 has demonstrated the ability to suppress tumor progression in intrahepatic cholangiocarcinoma, ovarian cancer, and lung cancer, often by sensitizing cells to chemotherapy or inducing ferroptosis. It has also shown therapeutic potential in models of Rett syndrome, diabetic nephropathy, and high-salt-induced endothelial dysfunction by restoring O-GlcNAc homeostasis.