Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETDZD-8Cat.No.:HY-11012CASNo.:327036-89-5Synonyms:GSK-3βInhibitorI;NP01139分?式:C??H??N?O?S分?量:222.26作?靶點(diǎn):GSK-3作?通路:PI3K/Akt/mTOR;StemCell/Wnt儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(449.92mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM4.4992mL22.4962mL44.9924mL5mM0.8998mL4.4992mL8.9985mL10mM0.4499mL2.2496mL4.4992mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(11.25mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(11.25mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(11.25mM);ClearsolutionBIOLOGICALACTIVITY?物活性TDZD-8GSK-3β的抑制劑，IC50為2μM；TDZD-8對(duì)Cdk-1/cyclinB，CK-II，PKA和PKC的作?較弱，IC50值均>100μM。IC50&TargetGSK-3β2μM(IC50)體外研究TDZD8resultsinasignificantdeclineofcellularATPlevelsinPC-3cells.TDZD8(10μM)treatmentalsotriggersadrasticautophagyresponseandAMPKactivationinPC-3cells.Furthermore,TDZD8(10μM)reducesmTORphosphorylationlevelsattheS2448site.Inaddition,TDZD8(10μM)inducesLKB1nuclear-cytoplasmtranslocation[3].體內(nèi)研究TDZD-8(TDZD8,1?or2?mg/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(0.5?mg/kg).L-dopa(25?mg/kg)plusbenserazide-HCl(6.25?Administration[2]mg/kg)aregivenonce-daily.TDZD8,anon-ATPcompetitiveinhibitorofGSK-3β,isdissolvedin10%DMSOandisadministeredi.p.(TDZD8-Lgroup,1?mg/kg;TDZD8-Hgroup,2?mg/kg,respectively)30?minpriortoL-dopaintakefor3weeks.(±)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diolhydrochloride(SKF38393),aD1Dopaminereceptoragonist,isdissolvedinsalineandisadministeredi.p.(SKF38393-L2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEgroup,5?mg/kg;SKF38393-Hgroup,10?mg/kg,respectively)30?minpriortoL-dopaintakefor3weeks[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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