327036-89-5
327036-89-5 structure
- Name: TDZD-8
- Chemical Name: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione
- CAS Number: 327036-89-5
- Molecular Formula: C10H10N2O2S
- Molecular Weight: 222.264
- Catalog: Biochemical Inhibitor PI3K/Akt/mTOR inhibitor (PI3K/Akt/mTOR) GSK-3 inhibitor
- Create Date: 2018-12-07 10:25:43
- Modify Date: 2024-01-02 18:39:43
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TDZD-8 is an inhibitor of GSK-3β, with an IC50 of 2 μM; TDZD-8 shows less potent activities against Cdk-1/cyclin B, CK-II, PKA, and PKC, with all IC50s of >100 μM.
| Name | 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione |
|---|---|
| Synonyms |
cc-646
1,2,4-Thiadiazolidine-3,5-dione, 2-methyl-4-(phenylmethyl)- NP12 GSK-3beta Inhibitor I TDZD-8 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione |
| Description | TDZD-8 is an inhibitor of GSK-3β, with an IC50 of 2 μM; TDZD-8 shows less potent activities against Cdk-1/cyclin B, CK-II, PKA, and PKC, with all IC50s of >100 μM. |
|---|---|
| Related Catalog | |
| Target |
GSK-3β:2 μM (IC50) |
| In Vitro | 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[3]. |
| In 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. TDZD8 treatment of 21 days induces a significant reduction in PKA expression in rats with established dyskinesia. Moreover, TDZD8 reduces FosB mRNA level in the striatum and lowers the expression of PPEB mRNA to similar levels as in 6-OHDA-lesioned rats without treated with L-dopa. The decrease in dyskinesia induced by TDZD8 is overcome by dopamine rceptor-1 agonist[2]. |
| Kinase 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[1]. |
| Animal Admin | Apomorphine hydrochloride is administered (0.5 mg/kg). L-dopa (25 mg/kg) plus benserazide-HCl (6.25 mg/kg) are given once-daily. TDZD8, a non-ATP competitive inhibitor of GSK-3β, is dissolved in 10% DMSO and is administered i.p. (TDZD8-L group, 1 mg/kg; TDZD8-H group, 2 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks. (±)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393), a D1 Dopamine receptor agonist, is dissolved in saline and is administered i.p. (SKF38393-L group, 5 mg/kg; SKF38393-H group, 10 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks[2]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 335.5±35.0 °C at 760 mmHg |
| Melting Point | 63-64.4ºC |
| Molecular Formula | C10H10N2O2S |
| Molecular Weight | 222.264 |
| Flash Point | 156.7±25.9 °C |
| Exact Mass | 222.046295 |
| PSA | 72.24000 |
| LogP | 0.30 |
| Vapour Pressure | 0.0±0.7 mmHg at 25°C |
| Index of Refraction | 1.646 |
| Storage condition | 2-8°C |
| Water Solubility | DMSO: 18 mg/mL |
| Symbol |
GHS08 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H334 |
| Precautionary Statements | P261-P342 + P311 |
| Personal Protective Equipment | dust mask type N95 (US);Eyeshields;Faceshields;Gloves |
| Hazard Codes | Xi: Irritant; |
| Risk Phrases | 43 |
| Safety Phrases | 36/37 |
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |
| HS Code | 2934999090 |
| HS Code | 2934999090 |
|---|---|
| Summary | 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |