Tideglusib-NP031112-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETideglusibCat. No.: HY-14872CAS No.: 865854-05-3Synonyms: NP031112分式: CHNOS分量: 334.39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 : 12.5 mg/mL (3

2、7.38 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.9905 mL 14.9526 mL 29.9052 mL5 mM 0.5981 mL 2.9905 mL 5.9810 mL10 mM 0.2991 mL 1.4953 mL 2.9905 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。BIOLOGICAL ACTIVITY物活性 Tideglusib (NP031112)種不可逆的 GSK-3 抑制劑，抑制 GSK-3

3、WT 和GSK-3C199A 的 IC50 分別為5nM，60 nM。IC50 & Target GSK-3(WT) GSK-3(C199A)5 nM (IC50) 60 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Tideglusib (NP12) is a small heterocyclic thiadiazolidinone (TDZD) derivative, which is an ATP-noncompetitive inhibitor of GSK-3 with an IC50 value in

4、the micromolar range 2. Incubation of both astrocyteand microglial cultures with Tideglusib (NP031112) completely abrogates the induction of TNF- and COX-2expression after glutamate treatment. These effects of NP031112 are not caused by a loss of cell viability,because the 24 h exposure of astrocyte

5、 and microglial cells to this TDZD does not modify cell viability 3.體內(nèi)研究 Tideglusib (NP12) treatment correlates with an increase of 46% as an average in the inhibitoryphosphorylation of GSK-3 at Ser-9 in the brains of APPsw-tauvlw mice, and the levels of the inactive from ofthe enzyme in NP12 treate

6、d mice are comparable to those found in wild-type littermate controls (p=0.893)(n=6-8 for each treatment). NP12 treatment results in significantly decreased phosphorylation at the putativeGSK-3-directed sites Ser-202 (CP13) and Ser-396/404 (PHF-1) in 15-month-old mice by more than 60%(p=0.023 and p=

7、0.024, respectively) 2. Injection of Tideglusib (NP031112) (50 mg/kg) into the rathippocampus dramatically reduces kainic acid-induced inflammation, as measured by edema formation usingT2-weighted magnetic resonance imaging and glial activation and has a neuroprotective effect in thedamaged areas of

8、 the hippocampus 3.PROTOCOLKinase Assay 1 35STideglusib (207 Bq/nmol) at 55 M is incubated with 5 M GSK-3 for 1 h at 25C in 315 L of 50 mMTris-HCl, pH 7.5, containing 150 mM NaCl and 0.1 mM EGTA. The incubation is extended for another 30 minafter having added 35 L of the same buffer with or without

9、100 mM DTE. Samples are then processed inthree different ways. First, an aliquot of 125 L of each sample is mixed with 375 L of 8 M GdnHCl in H2Oand heated at 80C for 5 min. A second aliquot of 125 L is diluted up to 500 L with H2O and left at roomtemperature for 5 min. In both cases, the free drug

10、is removed afterwards by gel filtration through SephadexG-25, and the amount of bound drug is determined by liquid scintillation counting on a 1450-MicroBeta TriLuxcounter. Finally, a third 40 L aliquot of each original sample is mixed with 10 L of denaturingelectrophoresis sample buffer without red

11、ucing agents, and 35 L of this mixture is loaded onto a 10%polyacrylamide gel and subjected to SDS(again in the absence of reducing agents except for the DTEalready included in the corresponding sample), followed by fluorography of the dried gel 1.MCE has not independently confirmed the accuracy of

12、these methods. They are for reference only.Animal Mice 2Administration 23 Groups of APPsw-tauvlw mice are administered Tideglusib (n=10-11 for each age) or vehicle (n=10-11 foreach age) starting at 9 months and 12 months of age during consecutive 3 months and used for subsequentclinicopathological a

13、nalyses. Tideglusib is administered at a daily dose of 200 mg/kg. Groups of age andgender-matched wild-type littermate controls (n=10 for each age) receive vehicle alone on a similar timetableschedule. Rats 3Adult male Wistar rats (8-12 weeks old) are used in this study. Rats (n5 per group) are anes

14、thetized byintraperitoneal injection of ketamine (60 mg/kg) and Domtor (5 g/kg) and placed into a stereotaxicapparatus. KA (1 g in 2.5 L PBS) alone or in combination with Tideglusib (2 ng in 2.5 L PBS) is injectedinto the hippocampus. Control animals of the same age are injected with vehicle.MCE has

15、 not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Int J Clin Exp Pathol. 2017;10(3):3033-3042. Harvard Medical School LINCS LIBRARYSee more customer

16、validations on HYPERLINK / www.MedChemEREFERENCES1. Domnguez JM, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3 by tideglusib. J Biol Chem, 2012, 287(2), 893-902. Sereno L, et al. A novel GSK-3beta inhibitor reduces Alzheimers pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009Sep;35(3):359-67.3. Luna-Medina R, et al. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxicconditions: potential therapeutic role in br