| CAS |
1009816-48-1 |
| English Name |
Thiamet G |
| Synonyms |
;ThiametG0nDiscontinued;ThiametG; |
| Molecular Formula |
C9H16N2O4S |
| Molecular Weight |
248.3 |
| Solubility |
Soluble in Water/DMSO ≥1mg/mL(Need ultrasonic) |
| Purity |
≥98% |
| Appearance |
White to light yellow Solid |
| Storage |
Powder:-20℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD15144964 |
| SMILES |
O[C@H]1[C@H](O)[C@@]2([H])N=C(NCC)S[C@@]2([H])O[C@@H]1CO |
| InChIKey |
PPAIMZHKIXDJRN-FMDGEEDCSA-N |
| InChI |
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 |
| PubChem CID |
135566354 |
| Target Point |
O-GlcNAcase |
| Passage |
Metabolic Enzyme&Protease |
| Background |
Thiamet G is a potent and selective inhibitor of O-GlcNAcase. |
| Biological Activity |
Thiamet G is a potent and selective inhibitor of O-GlcNAcase (OGA)， which acts to remove O-GlcNAc from modified proteins， with Ki of 20 nM for human OGA.[1-3] |
| IC50 |
Ki: 20nM(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]. |
| Cell Experiment |
Jurkat cells are seeded at 6000 cells/well in a 96-well plate，and 12 h later，cells are treated with compounds for the indicated time. Cell viability is determined by XTT assay.[3] |
| Animal Experiment |
For the Thiamet G dose dependence study，six 23-day-old male C57BL/6 mice receive single intraperitoneal injections of either 0，10，20，100，200，or 500 mg/kg of Thiamet G dissolved in PBS and then are euthanized 8 h later to evaluate the O-GlcNAc levels in different tissues(brain，liver，muscle，and knee). The time of sacrifice is chosen on the basis of previously published data on Thiamet G in rodents，which demonstrates that the peak level of O-GlcNAc proteins following administration of the drug is achieved after 8-10 h. Tissues are collected immediately after sacrifice，flash-frozen in liquid nitrogen，and stored at 80°C until required for use.[2] |
| Kinase Experiment |
All enzymatic assays are performed in triplicate at 37°C using 4-methylumbelliferyl N-acetyl-β-d-glucosaminide dehydrate as substrate. 1 nM of purified OGA is incubated with the compounds for 5 min，and then 0.2 mM of the substrate is added. The liberation of 4-methylumbellifery is monitored by kinetic reading at excitation/emission 355/460 nm using a Tecan M200 plate in a mode of 60 s/cycle and 15 cycles in total.[3] |
| Data Literature Source |
[1]. Yuzwa SA，et al. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol. 2012 Feb 26;8(4):393-9.
[2]. Andrés-Bergós J，et al. The increase in O-linked N-acetylglucosamine protein modification stimulates chondrogenic differentiation both in vitro and in vivo. J Biol Chem. 2012 Sep 28;287(40):33615-28.
[3]. Ding N，et al. Thiamet-G-mediated inhibition of O-GlcNAcase sensitizes human leukemia cells to microtubule-stabilizing agent NSC 125973. Biochem Biophys Res Commun. 2014 Oct 24;453(3):392-7. |
| Unit |
Bottle |
| Specification |
5mg 10mg 25mg |
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