Thiamet G
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MedKoo CAT#: 563409

CAS#: 1009816-48-1

Description: Thiamet G is a potent and selective inhibitor of O-GlcNAcase.


Chemical Structure

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Thiamet G
CAS# 1009816-48-1

Theoretical Analysis

MedKoo Cat#: 563409
Name: Thiamet G
CAS#: 1009816-48-1
Chemical Formula: C9H16N2O4S
Exact Mass: 248.08
Molecular Weight: 248.290
Elemental Analysis: C, 43.54; H, 6.50; N, 11.28; O, 25.77; S, 12.91

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 190 Ready to ship
50mg USD 350 Ready to ship
100mg USD 550 Ready to ship
200mg USD 950 Ready to ship
500mg USD 1950 Ready to ship
1g USD 2850 Ready to ship
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Synonym: Thiamet G; Thiamet-G;

IUPAC/Chemical Name: (3aR,5R,6S,7R,7aR)-2-(Ethylamino)-3a,6,7,7a-tetrahydro-5-(hydroxymethyl)-5H-pyrano[3,2-d]thiazole-6,7-diol

InChi Key: PPAIMZHKIXDJRN-FMDGEEDCSA-N

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

SMILES Code: O[C@H]1[C@H](O)[C@@]2([H])N=C(NCC)S[C@@]2([H])O[C@@H]1CO

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

More Info:

Biological target: 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.
In vitro activity: To further confirm the effect of TMG (Thiamet G ) on polarization of microglia, a polarization experiment was carried out in BV2 cells with or without TMG. BV2 cells were cultivated in medium containing M1 or M2 polarization cytokines in the presence of TMG. After 12 h, no significant change of M2 was observed in TMG-treated groups compared with the MCAO group, although M1 polarization was suppressed by TMG (Figure 5(a) to (d)). These results provide further evidence to assert that TMG influences microglial polarization. The transcriptional activity of NF-κB was also examined during polarization. The data showed that NF-κB was suppressed along with the decreased M1 phenotype trigged by TMG treatment (Figure 5(e) to (h)). After intervention with TMG, less p65 translocated into nuclei even when the amount of p65 in the cytoplasm did not change dramatically, which indicated that the transcriptional activity of p65 was suppressed by TMG (Figure 5(e) and (g), cytoplasmic: 0.52 ± 0.02 in the TMG group vs. 0.45 ± 0.01 in the Control group, ns: not significant, n = 9 per group; Figure 5(f) and (h), nuclear: 0.81 ± 0.06 in TMG group vs. 1.33 ± 0.01 in the Control group, P < 0.05, n = 9 per group). The implication was that TMG may shift the polarization of microglia/macrophages by inhibiting NF-κB activation. Reference: J Cereb Blood Flow Metab. 2017 Aug; 37(8): 2938–2951. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536801/
In vivo activity: To assess the effect of TMG (Thiamet G ) on the brain injury after focal ischemia in mice, infarct volumes and neurological deficit scores were quantified at several doses and multiple time points after MCAO. Higher doses (10–40 mg/kg) significantly reduced infarct volumes (Figure 1(a)). These decreases of infarct volume reached significance at 72 h after I/R injury, although the decreased mNSS reached significance at 24 h (Supplemental Figure 1). The following experiments were performed at a dose of 20 mg/kg TMG, and infarct volume was evaluated at 72 h after MCAO. To evaluate the effect of TMG on neuronal function of mice after MCAO, a variety of behavior function tests were executed. All these tests were performed at 24 h after MCAO. Results from mNSS testing exemplified a dramatic change in the MCAO group compared to both TMG-treated groups: 9 (6.5–10.5) in the preventative treatment group vs. 13 (10.5–13.5) in the MCAO group, P < 0.05, n = 9 per group; 6 (4.5–8) in the therapeutic treatment group vs. 13 (10.5– 13.5) in MCAOs, P < 0.01, n = 9 per group (Figure 1(d)). Further functional analyses with the foot-fault test, adhesion-removal test, and inclined plane test also indicated markedly improved outcomes after treatment with TMG in MCAO mice (Figure 1(e) to (g)). Together, these results support the presumption that treatment with TMG is neuroprotective in MCAO mice. Results shown in Figure 1(b) and (c) indicate that treatment with TMG before ischemic injury significantly reduced the infarct size (37.00 ± 0.60 mm3 in the preventative treatment group vs. 52.44 ± 1.00 mm3 in the MCAO group, P < 0.05, n = 9 per group). The therapeutic treatment group yielded virtually the same result (38.11 ± 1.60 mm3 vs. 52.44 ± 1.00 mm3 in the MCAO group, P < 0.05, n = 9 per group). Reference: J Cereb Blood Flow Metab. 2017 Aug; 37(8): 2938–2951. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536801/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 32.0 128.99
H2O 50.0 201.55

Preparing Stock Solutions

The following data is based on the product molecular weight 248.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Takeuchi T, Horimoto Y, Oyama M, Nakatani S, Kobata K, Tamura M, Arata Y, Hatanaka T. Osteoclast Differentiation Is Suppressed by Increased O-GlcNAcylation Due to Thiamet G Treatment. Biol Pharm Bull. 2020;43(10):1501-1505. doi: 10.1248/bpb.b20-00221. PMID: 32999159. 2. He Y, Ma X, Li D, Hao J. Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling. J Cereb Blood Flow Metab. 2017 Aug;37(8):2938-2951. doi: 10.1177/0271678X16679671. Epub 2016 Jan 1. PMID: 27864466; PMCID: PMC5536801. 3.Jiang M, Yu S, Yu Z, Sheng H, Li Y, Liu S, Warner DS, Paschen W, Yang W. XBP1 (X-Box-Binding Protein-1)-Dependent OGlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G. Stroke. 2017 Jun;48(6):1646-1654. doi: 10.1161/STROKEAHA.117.016579. Epub 2017 May 9. PMID: 28487326; PMCID: PMC5493893.
In vitro protocol: 1. Takeuchi T, Horimoto Y, Oyama M, Nakatani S, Kobata K, Tamura M, Arata Y, Hatanaka T. Osteoclast Differentiation Is Suppressed by Increased O-GlcNAcylation Due to Thiamet G Treatment. Biol Pharm Bull. 2020;43(10):1501-1505. doi: 10.1248/bpb.b20-00221. PMID: 32999159. 2. He Y, Ma X, Li D, Hao J. Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling. J Cereb Blood Flow Metab. 2017 Aug;37(8):2938-2951. doi: 10.1177/0271678X16679671. Epub 2016 Jan 1. PMID: 27864466; PMCID: PMC5536801.
In vivo protocol: 1. He Y, Ma X, Li D, Hao J. Thiamet G mediates neuroprotection in experimental stroke by modulating microglia/macrophage polarization and inhibiting NF-κB p65 signaling. J Cereb Blood Flow Metab. 2017 Aug;37(8):2938-2951. doi: 10.1177/0271678X16679671. Epub 2016 Jan 1. PMID: 27864466; PMCID: PMC5536801. 2. Jiang M, Yu S, Yu Z, Sheng H, Li Y, Liu S, Warner DS, Paschen W, Yang W. XBP1 (X-Box-Binding Protein-1)-Dependent OGlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G. Stroke. 2017 Jun;48(6):1646-1654. doi: 10.1161/STROKEAHA.117.016579. Epub 2017 May 9. PMID: 28487326; PMCID: PMC5493893.

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