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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
TDZD-8 (NP01139; GSK3 Inhibitor I) is a novel, potent and non-ATP competitive GSK-3β (glycogen synthase kinase-3beta) inhibitor with the potential for treating neurodegenerative diseases such as PD (parkinson disease). With an IC50 of 2 M, it inhibits GSK-3 and has negligible effects on CDK1, casein kinase II, PKA, and PKC. By preventing GSK-3beta activity, TDZD-8 defends the brain against I/R damage. TDZD-8 also exhibited strong antiproliferative activity in vitro and high antitumor efficacy in vivo, suggesting potential antitumor activity. In vitro, glioblastoma cell proliferation was reduced and apoptosis was induced in GL261 cells. In vivo, tumor growth was postponed and animal survival was improved by TDZD-8. These outcomes were connected to early ERK pathway activation, elevated EGR-1 and p21 gene expression, and extracellular signal-regulated kinase (ERK) pathway activation.
| Targets |
GSK-3β ( IC50 = 2 μM )
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|---|---|
| ln Vitro |
TDZD-8 acts as a noncompetitive inhibitor of ATP or GS-1 binding. In kinase assays, TDZD-8 exhibits no inhibition of PKA, PKC, Cdk-1/cyclin B, or CK-II. Primary leukemia specimens specifically experience cell death brought on by TDZD-8. Leukemia stem and progenitor cells are destroyed by TDZD-8. Oxidative stress is brought on by TDZD-8 treatment. Rapid cell death kinetics caused by TDZD-8's induction of cell death demonstrate a loss of membrane integrity. PKC and FLT3 are inhibited by TDZD-8 in primary AML specimens.
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| ln Vivo |
TDZD-8 (TDZD8, 1 or 2 mg/kg, i.p.) both reduces the induction of p-DARPP32 following chronic L-dopa treatment in parkinsonian animals. In rats with established dyskinesia, a 21-day treatment with TDZD8 results in a significant decrease in PKA expression. Additionally, TDZD8 lowers the expression of PPEB mRNA and FosB mRNA in the striatum to levels comparable to those of 6-OHDA-lesioned rats not receiving L-dopa treatment. Dopamine rceptor-1 agonist overrides the reduction in dyskinesia brought on by TDZD8.
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| Enzyme Assay |
GSK-3 activity is assayed in 50 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 1 mM EGTA, and 1 mM EDTA buffer, at 37°C, in the presence of 15 μM GS-1 (substrate), 15 μM [γ-32P]ATP in a final volume of 12 μL. After 20 min incubation at 37°C, 4 μL aliquots of the supernatant are spotted onto 2×2 cm pieces of Whatman P81 phosphocellulose paper, and 20 s later, the filters are washed four times (for at least 10 min each time) in 1% phosphoric acid. The dried filters are transferred into scintillation vials, and the radioactivity is measured in a liquid scintillation counter. Blank values are subtracted, and the GSK-3β activity is expressed in picomoles of phosphate incorporated in GS-1 per 20 min or in percentage of maximal activity.
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| Cell Assay |
TDZD8 results in a significant decline of cellular ATP levels in PC-3 cells. TDZD8 (10 μM) treatment also triggers a drastic autophagy response and AMPK activation in PC-3 cells. Furthermore, TDZD8 (10 μM) reduces mTOR phosphorylation levels at the S2448 site. In addition, TDZD8 (10 μM) induces LKB1 nuclear-cytoplasm translocation.
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| Animal Protocol |
NOD/SCID mouse
1 or 2 mg/kg i.p. |
| References |
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| Additional Infomation |
TDZD-8 is a member of the class of thiadiazolidines that is 1,2,4-thiadiazolidine-3,5-dione which is substituted by a methyl group at position 2 and by a benzyl group at position 4. It is a non-ATP competitive inhibitor of glycogen synthase kinase 3beta (GSK3beta). An experimental compound which was being developed for the potential treatment of Alzheimer's disease. It has a role as an EC 2.7.11.26 (tau-protein kinase) inhibitor, an apoptosis inducer, an antineoplastic agent, a neuroprotective agent and an anti-inflammatory agent. It is a thiadiazolidine and a member of benzenes.
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| Molecular Formula |
C10H10N2O2S
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|---|---|
| Molecular Weight |
222.2636
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| Exact Mass |
222.046
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| Elemental Analysis |
C, 54.04; H, 4.53; N, 12.60; O, 14.40; S, 14.43
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| CAS # |
327036-89-5
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| Related CAS # |
327036-89-5
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| PubChem CID |
4124851
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
335.5±35.0 °C at 760 mmHg
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| Melting Point |
63-64.4ºC
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| Flash Point |
156.7±25.9 °C
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| Vapour Pressure |
0.0±0.7 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
0.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
277
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CC2=CC=CC=C2)N(C)SC1=O
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| InChi Key |
JDSJDASOXWCHPN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H10N2O2S/c1-11-9(13)12(10(14)15-11)7-8-5-3-2-4-6-8/h2-6H,7H2,1H3
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| Chemical Name |
4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione
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| Synonyms |
NP 01139; NP01139; NP-01139; NP 01139; TDZD-8;TDZD8; TDZD 8; GSK3 Inhibitor I
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~44.5 mg/mL (200.2 mM)
Water: <1 mg/mL Ethanol: 44.5 mg/mL (200.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4992 mL | 22.4962 mL | 44.9924 mL | |
| 5 mM | 0.8998 mL | 4.4992 mL | 8.9985 mL | |
| 10 mM | 0.4499 mL | 2.2496 mL | 4.4992 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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