Thiamet G

Hyperphosphorylation of the tau protein leads to its aggregation and formation of neurofibrillary tangles, a hallmark of Alzheimer's disease and other tauopathic, neurodegenerative disorders. Tau is also dynamically modified by the addition and cleavage of O-linked beta-N-acetylglucosamine (O-GlcNAc) moieties, which is mediated in part by O-GlcNAcase. Levels of O-GlcNAcylated proteins from Alzheimer's disease brain extracts are decreased as compared to that in controls, suggesting that impaired brain glucose metabolism may contribute to pathogenesis. Thiamet G is a potent and selective inhibitor of O-GlcNAcase that demonstrates a Ki value of 21 nM. It increases cellular O-GlcNAc-modified protein levels (EC50 = 30 nM) and blocks phosphorylation of tau protein both in cultured PC-12 cells and in rats (200 mg/kg/day). Thiamet G is the first highly potent O-GlcNAcase inhibitor known to be orally bioavailable and effectively cross the blood brain barrier.Formal Name: 2-(ethylamino)-3aR,6S,7R,7aR-tetrahydro-5R-(hydroxymethyl)-5H-pyrano[3,2-d]thiazole-6,7-diol. CAS Number: 1009816-48-1. Molecular Formula: C9H16N2O4S. Formula Weight: 248.3. Purity: >97%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMSO: 20 mg/ml, Ethanol: 0.5 mg/ml, PBS (pH 7.2): 3 mg/ml. SMILES: [H][C@@]12[C@@](N=C(N(CC)[H])S2)([H])[C@@H](O)[C@H](O)[C@@H](CO)O1. InChi Code: InChI=1S/C9H16N2O4S/c1-2-10-9-11-5-7(14)6(13)4(3-12)15-8(5)16-9/h4-8,12-14H,2-3H2,1H3,(H,10,11)/t4-,5-,6-,7-,8-/m1/s1. InChi Key: PPAIMZHKIXDJRN-FMDGEEDCSA-N.