OSMI-1 is an O-GlcNAc transferase (OGT) inhibitor (IC50=2.7 μM) that is orally active and cell-permeable. OSMI-1 inhibits protein O-GlcNA acetylation without qualitatively altering cell-surface N- or O- linked glycans.

OGT:2.7 μM

METHODS: COS7 and Hela cells were treated with OSMI-1 (2-100 µM) for 24 h. Cell viability was measured using the CCK8 Assay.
RESULTS: 50 µM OSMI-1 reduced cell viability by more than 50%. [1]
METHODS: CHO cells were treated with OSMI-1 (10-100 µM) for 24 h, and the expression levels of target proteins were detected by Western Blot.
RESULTS: OSMI-1 reduced global OGlcNAcylation in a dose-dependent manner, with a maximum effect at 50 µM. [2]

METHODS: To assay antitumor activity in vivo, OSMI-1 (1 mg/kg, i.v.) and TRAIL (500 µg/kg, intraperitoneally) were administered to BALB/c-Foxn1nu/ArcGem nude mice harboring human colorectal carcinoma tumor HCT116 once daily for three weeks.
RESULTS: Tumor size was slightly reduced in mice treated with OSMI-1 or TRAIL alone, but significantly reduced in the OSMI-1 and TRAIL combination group. The combination treatment synergistically increased the antitumor activity of transplanted tumors in HCT116 nude mice. [3]
METHODS: To investigate the protective effect against Stx-mediated pathogenic responses, OSMI-1 (300-1000 µg/mouse in water containing 4.5% DMSO and 5% Tween 80) was injected intraperitoneally into Stx2a-attacked C57BL/6 mice once daily for seven days.
RESULTS: O-GlcNAc inhibition ameliorated the mortality and various disease symptoms induced by Stx2a exposure in mice, which was further enhanced by O-GlcNAc inhibition. [4]