H3R-antagonist-4-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEH3Rantagonist4Cat.No.:HY-162812分⼦式:C₃₀H₃₆N₂O₉分⼦量:568.61作⽤靶点:Apoptosis;Cholinesterase(ChE);TauProtein;Ferroptosis;HistamineReceptor作⽤通路:Apoptosis;NeuronalSignaling;GPCR/GProtein;Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性H3Rantagonist4(compound11l)胆碱酯酶和组胺H3受体(H3R)的双重抑制剂，对应的IC50分别为7.04μM(eeAChE)，9.73μM(hAChE)(可逆)，1.09nM(H3R)。H3Rantagonist4对⾃⾝和Cu2+诱导的Aβ1-42聚集有良好的抑制作⽤(95.48%和88.63%)，和对⾃⾝和Cu2+诱导的Aβ1-42原纤维具有良好的降解作⽤(80.16%和89.30%)。H3Rantagonist4有螯合Cu2+、Zn2+、Al3+和Fe2+等⽣物⾦属的能⼒。H3Rantagonist4显著降低了Aβ1-42诱导的tau蛋⽩过度磷酸化，抑制RSL-3诱导的PC12细胞凋亡和铁死亡。H3Rantagonist4在hCMEC/D3和hPepT1-MDCK细胞中有最佳的⾎脑屏障通透性和肠道吸收特性。H3Rantagonist4可改利⽤东莨菪碱(HY-N0296)诱导的阿尔兹海默症⼩⿏模型的学习和记忆障碍[1]。IC50&TargethAChEEeAChEeqBCHE9.73μM(IC50)7.04μM(IC50)13.40~88μM(IC50)体外研究H3Rantagonist4(compound11l)inhibitedeeAChE,eqBuChEandhAChEwithIC50valuesof7.04μM,13.40μMand9.73μM,respectively[1].H3Rantagonist4combineswithAChEandoccupiesCAS,midgorgesiteandPAS.ItinteractswiththeactivesiteandperipheralanionsiteofhAChE,andcanbindbothCASandPASsitesastwo-siteAChEinhibitors[1].H3Rantagonist4inhibitedtheaggregationofAβ1-42inducedbyitselfandCu2+(95.48%and88.63%,respectively)(ThTfluorescenceassay),anddegradedtheAβ1-42fibrilsinducedbyitselfandCu2+(80.16%and89.30%,respectively)(TEM)[1].TheIC50ofH3Rantagonist4(TRFRET)was1.09nM[1].H3Rantagonist4(5μM,10μMand20μM)(WB)inhibitedabnormaltauphosphorylationinPC12cells[1].H3Rantagonist4(11μM)increasedthesurvivalrateofPC12(800μMH2O2)to75.66%,anddecreasedthelevelofROS.PC12cellswereprotectedfromH2O2bydecreasingROSaccumulation,andthepercentage1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEofapoptoticcellswassignificantlyincreasedto22.9%±0.36%[1].H3Rantagonist4(5,10,20μM)inhibitedRSL3-inducedirondeathinPC12cellsandsignificantlyincreasedcellviability.Theinducedinjuryincreasedthepermeabilityofblood-brainbarrierinvitro[1].H3Rantagonist4(UV-visspectrometry)cansequesterCu2+,Zn2+,Al3+andFe2+[1].H3Rantagonist4increasedPEPT1proteinexpressioninhPepT1-MDCKcells[1].H3Rantagonist4(0-80μM,1h)showedanti-inflammatoryeffectinBV-2cellsanddidnotaffectproliferation[1].WesternBlotAnalysis[1]CellLine:PC12Concentration:5,10,20μM;Aβ25-35IncubationTime:30minResult:Inhibitedtauhyperphosphorylation,therelativeproteinexpressionofp-Tau(Thr181)/Total-tausignificantlyincreased.ApoptosisAnalysis[1]CellLine:PC12Concentration:5,10,20μM;H2O2,800μM,4hIncubationTime:24hResult:ReducedtheapoptosisofPC12cells.CellViabilityAssay[1]CellLine:BV-2Concentration:0-80μM;LPS10μg/mL;treatedwithallresult.IncubationTime:1hResult:Reducedinflammation.CellViabilityAssay[1]CellLine:PC12Concentration:5,10,20µM;H2O2,800μM,4hIncubationTime:24hResult:Increasedcellviabilityto75.66%.体内研究H3Rantagonist4(compound11l)(2.5and5.0mg/kg)caneffectivelyimprovethepathologicalmorphological2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEchangesofnervecellsinducedbyscopolamine（HY-N0296），andcouldsignificantlyimprovethecognitivedeficitandspatialmemoryofADmodelmice[1].AnimalModel:ADmousemodel[1]Dosage:2.5and5.0mg/kgAdministration:Intraperitonealinjection(i.p.)Result:ReducedAChEactivityandAChlevelsincreasedintherivastigmine.Hematoxylinandeosin(HE)stainingshowedthathippocampalcellsinthemodelgroupwerelooselyarrangedanddisorganized,andthatthenumberofcellswasreduced.SignificantlyimprovedcognitivedeficitsandspatialmemoryinADmodelmice.AgoodpharmacokineticprofileofH3Rantagonist4wasconfirmedinaninvivostudy[1].AnimalModel:SDmousemodel(200-220g)[1]Dosage:Fastedfor12h;10and17mg/kgAdministration:Intravenousinjection(i.v.)Result:Goodblood-brainbarrierpermeability.AnimalModel:SDmousemodel[1]Dosage:1.25,2.5,5.0mg/kg;scopolamine,1.25mg/kg,IntraperitonealinjectionAdministration:i.g.Result:Shortenedtheescapelatencycomparedwiththemodelgroup.Improvedthelearningandmemoryabilityofscopolamine-injectedmice[1].REFERENCES[1].JiaoChen,etal.ScutellareinderivativeswithhistamineH3receptorantagonismandcholinesteraseinhibitorypotencyasmultitarget-directedligandsforpossibleAlzheimer'sdiseasetherapy.BioorganicChemis