Thiamet G (1009816-48-1) is a potent, selective inhibitor of O-GlcNAcase (Ki = 21 nM for human O-GlcNAcase). Increases levels of O-GlcNAc-modified proteins in cellular assays and in vivo. Suppresses phosphorylation of tau protein in rat cortex and hippocampus.1 Stabilizes tau against aggregation and slows neurodegeneration.2 Thiamet G prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.3 Elevates soluble tau species and reduces tauopathy in mouse models.4 Active in vivo and blood brain barrier permeable.
1) Yuzwa et al. (2008), A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo; Nat. Chem. Biol., 4 483
2) Yuzwa et al. (2012), Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation; Nat. Chem. Biol. 8 393
3) Yuzwa et al. (2014), Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice; Mol. Neurodegener., 9 42
4) Hastings et al. (2017) Inhibition of O-GlcNAcase leads to elevation of O-GlcNAc tau and reduction of tauopathy and cerebrospinal fluid tau in rTg4510 mice; Mol. Neurodegener., 12 39