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Chemical Structure| 1009816-48-1 Chemical Structure| 1009816-48-1

Structure of Thiamet G
CAS No.: 1009816-48-1

Chemical Structure| 1009816-48-1

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Thiamet G is a selective O-GlcNAcase inhibitor with an IC50 value of 21 nM. Thiamet G has neuroprotective and anti-inflammatory effects and can be used in research on Alzheimer’s disease and neurodegenerative disorders.

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Product Details of Thiamet G

CAS No. :1009816-48-1
Formula : C9H16N2O4S
M.W : 248.30
SMILES Code : O[C@H]1[C@H](O)[C@@]2([H])N=C(NCC)S[C@@]2([H])O[C@@H]1CO
MDL No. :MFCD15144964

Safety of Thiamet G

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317
Precautionary Statements:P261-P280

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Neuroblastoma N2a cells 5 µM 12 hours Thiamet-G (TG), an OGA inhibitor, increased O-GlcNAcylation of N2a cells in a dose-dependent manner without affecting cell viability. TG treatment also inhibited H2O2-induced apoptosis in N2a cells. Acta Pharmacol Sin. 2024 Apr;45(4):714-727.
BV2 cells 200 ng/mL 12 hours To evaluate the effect of TMG on M1 polarization of BV2 cells. Results showed that TMG treatment inhibited LPS-induced M1 polarization and reduced mRNA expression of pro-inflammatory cytokines (TNF-α, iNOS, IL-1β, IL-6, and MCP-1). J Cereb Blood Flow Metab. 2017 Aug;37(8):2938-2951.
RT4 cells 10 µM 16 hours To evaluate the effect of O-GlcNAcylation on autophagy in bladder cancer cells. Results showed that TG treatment increased O-GlcNAcylation and p62 levels and decreased LC3 II expression, indicating inhibition of autophagy. Cell Mol Biol Lett. 2020 Mar 10;25:17.
5637 cells 10 µM 16 hours To evaluate the effect of O-GlcNAcylation on autophagy in bladder cancer cells. Results showed that TG treatment increased O-GlcNAcylation and p62 levels and decreased LC3 II expression, indicating inhibition of autophagy. Cell Mol Biol Lett. 2020 Mar 10;25:17.
Cartilage endplate stem cells (CESCs) 1 µM 21 days Thiamet-G promoted osteogenic differentiation and inhibited chondrogenic differentiation of CESCs Stem Cell Res Ther. 2019 Nov 28;10(1):357.
Human rheumatoid arthritis synovial fibroblasts (RASFs) 1-5 µM 24 hours To evaluate the inhibitory effect of Thiamet G on IL-1β-induced IL-6 and IL-8 production, results showed that Thiamet G dose-dependently inhibited IL-1β-induced IL-6 and IL-8 production and increased the expression of O-GlcNAc-modified proteins. Front Immunol. 2022 Aug 10;13:928436.
BeWo human trophoblast cells 5 µM 24 hours TMG upregulated the expression of syncytiotrophoblast-associated transcription factors OVOL1 and GCM1 and the cell fusion gene ERVFRD1 Cells. 2020 Oct 6;9(10):2246.
Mouse blastocysts 5 µM 24 hours TMG increased O-GlcNAcylation levels, altered OGT and OGA localization, and promoted mouse blastocyst invasion of endometrial epithelium Cells. 2020 Oct 6;9(10):2246.
Human umbilical vein endothelial cells (HUVECs) 1 µM 24 hours TMG pretreatment reduced GSDMD-N protein levels, indicating that TMG may function by inhibiting GSDMD cleavage Inflamm Res. 2024 Jan;73(1):5-17.
HCT116 cells 1 µM 6 hours To study the response of OGT intron retention to O-GlcNAc levels Cell Rep. 2017 Aug 1;20(5):1088-1099.
293A-TOA cells 1 µM 6 hours To study the response of OGT intron retention to O-GlcNAc levels Cell Rep. 2017 Aug 1;20(5):1088-1099.
Primary mouse vascular smooth muscle cells (VSMC) 10 µM 6 hours Increased O-GlcNAcylation and promoted VSMC calcification Circ Res. 2014 Mar 28;114(7):1094-102.
HEK293 cells 32 nM (EC50) 6 hours To evaluate the effect of Thiamet G on O-GlcNAcylated protein levels, showing a dose-dependent increase in O-protein levels. Mol Neurodegener. 2017 May 18;12(1):39.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice DSS-induced colitis model Oral gavage 0.2 g/kg Once daily for 2 weeks Augmented intestinal epithelial O-GlcNAc signaling, alleviated chemical-induced colitis EMBO Mol Med. 2018 Aug;10(8):e8736
Mice R6/2 mouse model In vitro treatment 0.5uM 4 hours Thiamet-G significantly reduced cell death in primary cortical neurons transfected with HTT 82Q and rescued nucleocytoplasmic trafficking defects with the nuclear restoration of both endogenous Ran and exogenous NLS-tdTomato-NES. Neuron. 2017 Apr 5;94(1):93-107.e6
Mice C57BL/6J mice Intracranial injection 1 mM Single injection Injection of Thiamet G in the VTA and NAc facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Neurosci Bull. 2022 Mar;38(3):263-274
Rhesus monkeys Rhesus monkeys and OgaΔBr mice Intravenous injection 10 mg/kg Single dose, PET scan performed 45 minutes after administration To evaluate the inhibitory effect of Thiamet-G on OGA, results showed that Thiamet-G significantly reduced brain uptake of the radioligand, indicating high efficacy in inhibiting OGA. J Nucl Med. 2019 Jan;60(1):129-134
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice Xenograft tumor model Intraperitoneal injection 20 mg/kg Once daily for 24 days To study the effect of ISS deletion on tumor growth Cell Rep. 2017 Aug 1;20(5):1088-1099.
Mice Low-dose streptozotocin (STZ)-induced diabetic mouse model Intravenous injection 20 mg/kg Weekly for 2 months Increased vascular O-GlcNAcylation, accelerated vascular calcification and worsened aortic compliance Circ Res. 2014 Mar 28;114(7):1094-102.
C57BL/6 mice Middle cerebral artery occlusion (MCAO) model Intraperitoneal injection 20 mg/kg Preventive group: once daily for 3 days before surgery; Therapeutic group: starting at 0.5 h after surgery, once daily for 3 days To evaluate the neuroprotective effect of TMG in MCAO mice. Results showed that TMG significantly reduced infarct volume, improved neurological deficit scores, and modulated the expression of pro-inflammatory and anti-inflammatory cytokines. Additionally, TMG reduced the number of Iba1+ cells, decreased expression of M1 markers, and increased expression of M2 markers. J Cereb Blood Flow Metab. 2017 Aug;37(8):2938-2951.
Mice REM sleep deprivation (REMSD) model Intraperitoneal injection 20 mg/kg Daily for 72 hours Thiamet G restored REMSD-induced learning and memory impairment and dendritic spine density Neurotherapeutics. 2021 Oct;18(4):2504-2517
Mice Transient or permanent middle cerebral artery occlusion model Intraperitoneal or intravenous injection 30 mg/kg 18 hours before or 30 minutes after stroke induction Increased O-GlcNAcylation levels, improved stroke outcome in both young and aged mice Stroke. 2017 Jun;48(6):1646-1654
Mice Young mice (2-month-old) Intraperitoneal injection 30 mg/kg/day Once daily for 35 days To mimic age-related elevation of O-GlcNAc and study its effect on spermatogenesis. Results showed that high O-GlcNAcylation led to decreased sperm concentration, reduced testis weight and organ index, and impaired spermatogenesis. Cell Death Discov. 2023 May 15;9(1):163
RTg4510 mice Tauopathy model Oral 500 mg/kg/day Daily administration for 8 weeks To evaluate the effect of Thiamet G on tau pathology, showing that chronic Thiamet G treatment significantly reduced insoluble tau aggregates and phosphorylated tau species in the brain and decreased total tau levels in cerebrospinal fluid. Mol Neurodegener. 2017 May 18;12(1):39.
C57BL/6J mice LPS-induced sepsis model Intravenous injection 600 μg/kg Single dose, lasting 12 hours TMG treatment increased blood perfusion in the liver, mesentery, and lower limbs of mice and reduced vascular endothelial injury Inflamm Res. 2024 Jan;73(1):5-17.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.03mL

0.81mL

0.40mL

20.14mL

4.03mL

2.01mL

40.27mL

8.05mL

4.03mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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