TDZD-8-GSK-3β-Inhibitor-I-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETDZD-8Cat. No.: HY-11012CAS No.: 327036-89-5Synonyms: GSK-3 Inhibitor I; NP 01139分式: CHNOS分量: 222.26作靶點: GSK-3作通路: PI3K/Akt/mTOR; Stem Cell/Wnt儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO

2、: 100 mg/mL (449.92 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 4.4992 mL 22.4962 mL 44.9924 mL5 mM 0.8998 mL 4.4992 mL 8.9985 mL10 mM 0.4499 mL 2.2496 mL 4.4992 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再?/p>

3、次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (11.25 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (11.25 mM); Clear solution1/3 Master of

4、Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (11.25 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TDZD-8GSK-3 的抑制劑，IC50 為 2 M；TDZD-8 對 Cdk-1/cyclin B，CK-II，PKA 和 PKC 的作較弱，IC50 值均 100 M。IC50 & Target GSK-32 M (IC50)體外研究 TDZD8 results in a significant decline

5、 of cellular ATP levels in PC-3 cells. TDZD8 (10 M) treatment alsotriggers a drastic autophagy response and AMPK activation in PC-3 cells. Furthermore, TDZD8 (10 M)reduces mTOR phosphorylation levels at the S2448 site. In addition, TDZD8 (10 M) induces LKB1 nuclear-cytoplasm translocation 3.體內(nèi)研究 TDZ

6、D-8 (TDZD8, 1or 2mg/kg, i.p.) both reduces the induction of p-DARPP32 following chronic L-dopatreatment in parkinsonian animals. TDZD8 treatment of 21 days induces a significant reduction in PKAexpression in rats with established dyskinesia. Moreover, TDZD8 reduces FosB mRNA level in the striatumand

7、 lowers the expression of PPEB mRNA to similar levels as in 6-OHDA-lesioned rats without treated withL-dopa. The decrease in dyskinesia induced by TDZD8 is overcome by dopamine rceptor-1 agonist 2.PROTOCOLKinase Assay 1 GSK-3 activity is assayed in 50 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 1 mM EGTA, and

8、 1 mM EDTA buffer, at37C, in the presence of 15 M GS-1 (substrate), 15 M -32PATP in a final volume of 12 L. After 20 minincubation at 37C, 4 L aliquots of the supernatant are spotted onto 22 cm pieces of Whatman P81phosphocellulose paper, and 20 s later, the filters are washed four times (for at lea

9、st 10 min each time) in 1%phosphoric acid. The dried filters are transferred into scintillation vials, and the radioactivity is measured in aliquid scintillation counter. Blank values are subtracted, and the GSK-3 activity is expressed in picomoles ofphosphate incorporated in GS-1 per 20 min or in p

10、ercentage of maximal activity 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Apomorphine hydrochloride is administered (0.5mg/kg). L-dopa (25mg/kg) plus benserazide-HCl (6.25Administration 2 mg/kg) are given once-daily. TDZD8, a non-ATP compet

11、itive inhibitor of GSK-3, is dissolved in 10% DMSOand is administered i.p. (TDZD8-L group, 1mg/kg; TDZD8-H group, 2mg/kg, respectively) 30min 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 dis

12、solved in saline and is administered i.p. (SKF38393-Lgroup, 5mg/kg; SKF38393-H group, 10mg/kg, respectively) 30min prior to L-dopa intake for 3 weeks 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻2/3 Master of Small Molecules 您邊的抑制劑師www.M

13、edChemE Eur J Med Chem. 2017 Apr 19;135:370-381. Exp Cell Res. 2019 Aug.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Martinez A, et al. First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta) inhibitors: thiadiazolidinones (TDZD) aspotential drugs for the treat

14、ment of Alzheimers disease. J Med Chem. 2002 Mar 14;45(6):1292-9.2. Xie CL, et al. Inhibition of Glycogen Synthase Kinase-3 (GSK-3) as potent therapeutic strategy to ameliorates L-dopa-induceddyskinesia in 6-OHDA parkinsonian rats. Sci Rep. 2016 Mar 21;6:23527.3. Sun A, et al. GSK-3 controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate. 2016 Feb;