GSK3β-IN-4-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK3β-IN-4Cat.No.:HY-179723CASNo.:3083425-61-7分⼦式:C₂₆H₂₆N₄O₂分⼦量:426.51作⽤靶点:GSK-3;TauProtein作⽤通路:PI3K/Akt/mTOR;StemCell/Wnt;NeuronalSignaling储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性GSK3β-IN-4⼀种选择性、强效、具有⼝服活性且能穿透⾎脑屏障的ATP竞争性GSK3β抑制剂，其IC50值为0.37nM。GSK3β-IN-4对GSK3α的IC50值为2.75nM，SI为7.4。GSK3β-IN-4通过抑制GSK3β来减少Ser396位点的tau蛋⽩磷酸化，并能改阿尔茨海默病模型中的认知缺陷。GSK3β-IN-4可⽤于阿尔茨海默病的研究[1]。IC50&TargetGSK-3βGSK-3α0.37nM(IC50)2.75nM(IC50)体外研究GSK3β-IN-4(Compound39a)significantlyinhibitsTauphosphorylation(EC50=0.06μM)atSer396inTau(P301L)293Tcellswithlowcytotoxicity(IC50=80.75μM)[1].GSK3β-IN-4inhibitsGSK3βinanATP-competitivemannerwithIC50valuesof1.27nM,7.14nM,and77.8nMat1×Km,10×Km,and100×KmATPconcentrations,respectively[1].体内研究GSK3β-IN-4(Compound39a)(1000mg/kg,p.o.,singledose)showsnolethalityinC57BL/6Jmice,withnormalbodyweightgain,nobehavioralabnormalitieswithin14days,andnopathologicaldamageinmajororgans[1].GSK3β-IN-4(5-25mg/kg,p.o.,dailyfor14days)imorovescognitivedeficitsandtauSer396phosphorylationlevelsinanOkadaicacid(HY-N6785)-inducedmousemodelofAlzheimer'sdisease[1].GSK3β-IN-4(5mg/kg,p.o.,oncedailyfor60days)melioratesspatiallearningandmemoryimpairmentsin6-month-old3×Tg-ADmice,reducesTauSer396phosphorylationinthehippocampalCA3region,withefficacycomparabletoDonepezil(HY-14566)(5mg/kg),andshowsnoimpactonmotorfunction[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:C57BL/6Jmice(Okadaicacid-inducedmodelofAlzheimer'sdisease)[1]Dosage:5mg/kg,25mg/kgAdministration:OrallyadministrationResult:Reducedtauphosphorylation(pS396)inthehippocampusandtemporal.Reducedescapelatencyandimprovedspatialmemoryretention,asevidencedbyincreasedtimespentinthetargetquadrantandhigherplatform-crossingfrequency.Didnotcauselocomotordysfunction.AnimalModel:3×Tg-ADmice(transgenicmodelofAlzheimer'sdisease)[1]Dosage:5mg/kgAdministration:OrallyadministrationResult:Improvedspatiallearningandmemorydeficits.Reducedescapelatencyduringhiddenplatformtrialsandincreasedtimespentinthetargetquadrantduringprobetests.RevealedareductioninpS396taulevelsinthehippocampalCA3region.REFERENCES[1].LiuW,etal.Discoveryofnovelharminederivativesaspotent,selective,andbrainpermeableGSK3βinhibitorswitheffectiveInvivoanti-ADactivity.EurJMedChem.2026;303:118389.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalappli