TDZD-8-GSK-3β-Inhibitor-I-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETDZD-8Cat.No.:HY-11012CASNo.:327036-89-5Synonyms:GSK-3βInhibitorI;NP01139分⼦式:C₁₀H₁₀N₂O₂S分⼦量:222.26作⽤靶点:GSK-3作⽤通路:PI3K/Akt/mTOR;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(449.92mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM4.4992mL22.4962mL44.9924mL5mM0.8998mL4.4992mL8.9985mL10mM0.4499mL2.2496mL4.4992mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(11.25mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.25mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.25mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TDZD-8GSK-3β的抑制剂，IC50为2μM；TDZD-8对Cdk-1/cyclinB，CK-II，PKA和PKC的作⽤较弱，IC50值均>100μM。IC50&TargetGSK-3β2μM(IC50)体外研究TDZD8resultsinasignificantdeclineofcellularATPlevelsinPC-3cells.TDZD8(10μM)treatmentalsotriggersadrasticautophagyresponseandAMPKactivationinPC-3cells.Furthermore,TDZD8(10μM)reducesmTORphosphorylationlevelsattheS2448site.Inaddition,TDZD8(10μM)inducesLKB1nuclear-cytoplasmtranslocation[3].体内研究TDZD-8(TDZD8,1ꢀor2ꢀmg/kg,i.p.)bothreducestheinductionofp-DARPP32followingchronicL-dopatreatmentinparkinsoniananimals.TDZD8treatmentof21daysinducesasignificantreductioninPKAexpressioninratswithestablisheddyskinesia.Moreover,TDZD8reducesFosBmRNAlevelinthestriatumandlowerstheexpressionofPPEBmRNAtosimilarlevelsasin6-OHDA-lesionedratswithouttreatedwithL-dopa.ThedecreaseindyskinesiainducedbyTDZD8isovercomebydopaminerceptor-1agonist[2].PROTOCOLKinaseAssay[1]GSK-3activityisassayedin50mMTris-HCl,pH7.5,10mMMgCl2,1mMEGTA,and1mMEDTAbuffer,at37°C,inthepresenceof15μMGS-1(substrate),15μM[γ-32P]ATPinafinalvolumeof12μL.After20minincubationat37°C,4μLaliquotsofthesupernatantarespottedonto2×2cmpiecesofWhatmanP81phosphocellulosepaper,and20slater,thefiltersarewashedfourtimes(foratleast10mineachtime)in1%phosphoricacid.Thedriedfiltersaretransferredintoscintillationvials,andtheradioactivityismeasuredinaliquidscintillationcounter.Blankvaluesaresubtracted,andtheGSK-3βactivityisexpressedinpicomolesofphosphateincorporatedinGS-1per20minorinpercentageofmaximalactivity[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalApomorphinehydrochlorideisadministered(0.5ꢀmg/kg).L-dopa(25ꢀmg/kg)plusbenserazide-HCl(6.25ꢀAdministration[2]mg/kg)aregivenonce-daily.TDZD8,anon-ATPcompetitiveinhibitorofGSK-3β,isdissolvedin10%DMSOandisadministeredi.p.(TDZD8-Lgroup,1ꢀmg/kg;TDZD8-Hgroup,2ꢀmg/kg,respectively)30ꢀminpriortoL-dopaintakefor3weeks.(±)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diolhydrochloride(SKF38393),aD1Dopaminereceptoragonist,isdissolvedinsalineandisadministeredi.p.(SKF38393-L2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEgroup,5ꢀmg/kg;SKF38393-Hgroup,10ꢀmg/kg,respectively)30ꢀminpriortoL-dopaintakefor3weeks[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellDeathDiffer.2021Jan;28(1):337-348.•EurJMedChem.2017Apr19;135:370-381.•ExpCellRes.2019Oct15;383(2):111557.•ActaBiochimBiophysSin(Shanghai).2020Apr20;52(4):363-370.•HumExpToxicol.2021Mar25;9603271211002885.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MartinezA,etal.Firstnon-ATPcompetitiveglycogensynthasekinase3beta(GSK-3beta)inhibitors:thiadiazolidinones(TDZD)aspotentialdrugsforthetreatmentofAlzheimer'sdisease.JMedChem.2002Mar14;45(6):1292-9.[2].XieCL,etal.InhibitionofGlycogenSynthaseKinase-3β(GSK-3β)aspotenttherapeuticstrategytoamelioratesL-dopa-induceddyskinesiain6-OHDAparkinsonianrats.SciRep.2016Mar21;6:23527.[3].SunA,etal.GSK-3βcontrolsautophagybymodulatingLKB1-AMPKpathwayinprostatecancercells.Prost