H3R-antagonist-4-生命科學(xué)試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEH3Rantagonist4Cat.No.:HY-162812分?式:C??H??N?O?分?量:568.61作?靶點(diǎn):Apoptosis;Cholinesterase(ChE);TauProtein;Ferroptosis;HistamineReceptor作?通路:Apoptosis;NeuronalSignaling;GPCR/GProtein;Immunology/Inflammation儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性H3Rantagonist4(compound11l)膽堿酯酶和組胺H3受體(H3R)的雙重抑制劑，對(duì)應(yīng)的IC50分別為7.04μM(eeAChE)，9.73μM(hAChE)(可逆)，1.09nM(H3R)。H3Rantagonist4對(duì)??和Cu2+誘導(dǎo)的Aβ1-42聚集有良好的抑制作?(95.48%和88.63%)，和對(duì)??和Cu2+誘導(dǎo)的Aβ1-42原纖維具有良好的降解作?(80.16%和89.30%)。H3Rantagonist4有螯合Cu2+、Zn2+、Al3+和Fe2+等?物?屬的能?。H3Rantagonist4顯著降低了Aβ1-42誘導(dǎo)的tau蛋?過度磷酸化，抑制RSL-3誘導(dǎo)的PC12細(xì)胞凋亡和鐵死亡。H3Rantagonist4在hCMEC/D3和hPepT1-MDCK細(xì)胞中有最佳的?腦屏障通透性和腸道吸收特性。H3Rantagonist4可改利?東莨菪堿(HY-N0296)誘導(dǎo)的阿爾茲海默癥??模型的學(xué)習(xí)和記憶障礙[1]。IC50&TargethAChEEeAChEeqBCHE9.73μM(IC50)7.04μM(IC50)13.40~88μM(IC50)體外研究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?邊的抑制劑?師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%.體內(nèi)研究H3Rantagonist4(compound11l)(2.5and5.0mg/kg)caneffectivelyimprovethepathologicalmorphological2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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