hAChE-IN-8-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEhAChE-IN-8Cat.No.:HY-163514分⼦式:C₂₅H₂₂N₄O₄分⼦量:442.47作⽤靶点:Cholinesterase(ChE);DYRK作⽤通路:NeuronalSignaling;ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性hAChE-IN-8(CompoundS-12)⼝服有效的hAChE选择性的抑制剂(IC50=0.486μM)。hAChE-IN-8对BACE-1也有抑制效果(IC50=0.542μM)，对Dyrk1A抑制效果不明显(IC50>10μM)。hAChE-IN-8可以减少Aβ聚集，拥有良好的⾎脑屏障穿透性，具有⼝服活性。hAChE-IN-8主⽤于阿尔茨海默病的研究[1]。IC50&TargethBCHEDYRK1AhAChE0.542μM(IC50)>10μM(IC50)0.486μM(IC50)体外研究hAChE-IN-8(10-80μM;72h)isnottoxictoSH-SY5Yneuronalcellsathighconcentrations[1].hAChE-IN-8(40μM;72h)protectsSH-SY5YcellsfromAβ1-42-inducedoxidativestresswithsignificantlyincreaseinsurvivalandnormalizationofcellmorphology[1].hAChE-IN-8(5-20μM;48h)showssignificantanti-Aβaggregationactivity[1].体内研究hAChE-IN-8(500,1000mg/kg;p.o.;singledose)atthehighdoseshowsnotoxicityorabnormalresponseinallWistarratsduringthe14-dayobservationperiod[1].hAChE-IN-8(2.5-10mg/kg;p.o.;singledose)improvesscopolamine(HY-N0296)-inducedmemorylossinadose-dependentmanner.Showsantioxidantpotentialinscopolamine-inducedoxidativestressandrestoresAChandAChElevels[1].hAChE-IN-8(10mg/kg;p.o.;oncedailyfor9days)Aβ1-42showssignificantcognitiveimprovementintheAβ1-42inducedADmodel.SignificantlyreducesAD-relatedproteinlevels[1].hAChE-IN-8(10-200μM)isaddedtotheculturemediumofDrosophilaandshowsnosignificanttoxicitytoDrosophilaatlowerconcentrations,butexhibitssometoxicityathigherconcentrations[1].hAChE-IN-8(10-20μM)effectivelyrestoresAβ42-inducedocularphenotypicchangesintheDrosophilaADmodel,exhibitingsignificantneuroprotectiveeffects[1].hAChE-IN-8(5-50μM)exhibitsahighviabilityoflarvalcellsatlowerconcentrations,butathigher1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEconcentrationsthecellviabilitydecreasessignificantlyandexhibitssomecytotoxicity[1].PharmacokineticAnalysisinWistarrat[1]RouteDose(mg/kg)Tmax(h)Cmax(ng/mL)t1/2(h)MRT(h)AUC0-8(ng/mL.h)AUCtotal(ng/mL.h)p.o.109±1.041355±6.03341±1.01732±1.7131136.18±4.0171736.18±7.101AnimalModel:Wistarrats[1]Dosage:500,1000mg/kgAdministration:p.o.;singledoseResult:Atthemaximumdoseof1000mg/kg,thehistologyoforgans(kidney,liver,brainandheart)wasnormalinratsafter14days.AnimalModel:Scopolamine-inducedmemorylossinWistarrats[1]Dosage:2.5mg/kg,5mg/kg,10mg/kgAdministration:p.o.;singledoseResult:Theeffectofimprovementinthe10mg/kgdosegroupwassimilartodonepezil(HY-14566)group.DecreasedAChEactivity,increasedAChlevels,decreasedMDAlevels,andincreasedSOD,CAT,andGSHlevels.AnimalModel:Aβ1-42inducedADmode[1]Dosage:10mg/kgAdministration:p.o.;oncedailyfor9daysResult:Significantlyreducedescapelatency(ELT)andincreasednumberofplateaucrossings,similartothedonepezil(HY-14566)group.SignificantlyreducedBACE-1,α-synuclein,APPandTauproteinlevels.SignificantlyreducedBACE-1andAβlevelsintheDG,CA1andCA3regions.AnimalModel:ADDrosophilamodel[1]Dosage:10μM,20μMAdministration:/Result:Ataconcentrationof10μM,therecoveryoftheeyephenotypeinDrosophilawas21%.At20μM,therecoveryrateincreasedto57%.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].WaikerDK,etal.Design,synthesis,andbiologicalevaluationofsome2-(3-oxo-5,6-diphenyl-1,2,4-triazin-2(3H)-yl)-N-phenylacetamidehybridsasMTDLsforAlzheimer'sdiseasetherapy.EurJMedChem.2024May5;271:116409.McePdfHeightCaution: