Thiamet G

Thiamet G is a potent and selective inhibitor of O-GlcNAcase (OGA), which acts to remove O-GlcNAc from modified proteins, with K_i of 20 nM for human OGA. IC50 & Target: Ki: 20 nM (Human OGA)^[1] In Vitro: Thiamet G (1 μM) induces a clear increase in the accumulation of O-GlcNAcylated proteins of ATDC5 cells. O-GlcNAc accumulation induced by Thiamet G also evokes a clear increase in the activity of these MMPs. Thiamet G (1 μM) induces the phosphorylation of JNK, ERK, and p38 but not phosphorylation of Akt^[2]. Thiamet G (0.1-10 μM) does not significantly affect the cell viability. Thiamet G decreases phosphorylation of tau and alters the microtubule dynamics^[3]. In Vivo: Thiamet G (500 mg/kg/d) increases global and tau O-GlcNAc and reduces neurodegeneration. Thiamet G-treated group has 1.4-fold more motor neurons and hinders tau-driven neurodegeneration within this transgenic model. Thiamet G treatment therefore has no detectable effect on mice lacking the P301L transgene, indicating that prevention of neurodegeneration and weight loss is mediated by Thiamet G treatment only in the context of the P301L transgene. In Thiamet G-treated mice, the O-GlcNAc increases in the brain and spinal cord tissues^[1]. Thiamet G (20 mg/kg, i.p.) increases O-GlcNAc levels in brain, liver, and knee of the C57BL/6 mice in a dose-dependent manner^[2].