对乙酰氨基酚作用机制 - Medchemexpress - MCE中国

ProductDataSheetAcetaminophenCat.No.:HY-66005CASNo.:103-90-2分⼦式:C₈H₉NO₂分⼦量:151.16作⽤靶点:COX;HistoneAcetyltransferase;EndogenousMetabolite作⽤通路:Immunology/Inflammation;Epigenetics;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2years*该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤。溶解性数据体外实验DMSO:≥100mg/mL(661.55mM)H2O:10mg/mL(66.16mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.SolventMass1mg5mg10mgConcentration制备储备液1mM6.6155mL33.0775mL66.1551mL5mM1.3231mL6.6155mL13.2310mL10mM0.6616mL3.3078mL6.6155mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现⽤现配，即刻使⽤.体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶1.请依序添加每种溶剂：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(16.54mM);Clearsolution此⽅案可获得≥2.5mg/mL(16.54mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊

50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(16.54mM);Clearsolution此⽅案可获得≥2.5mg/mL(16.54mM，饱和度未知)的澄溶液。Page1of2www.MedChemE以1mL⼯作液为例，取100μL25.0mg/mL的澄均匀。DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶液中，混合3.请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(16.54mM);Clearsolution此⽅案可获得≥2.5mg/mL(16.54mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性Acetaminophen(Paracetamol)选择性环氧合酶-2(COX-2)的抑制剂，IC50值为25.8μM。Acetaminophen效的肝N-⼄酰转移酶2(NAT2)抑制剂。Acetaminophen⼴泛使⽤的解热和⽌痛剂[1][2][3][4]。⼀种有IC₅₀&TargetHumanEndogenousCOX-2COX-1Metabolite25.8μM(IC50)113.7μM(IC50)体外研究Invitro,acetaminophenelicitesa4.4-foldselectivitytowardCOX-2inhibition(IC50113.7μMforCOX-1;IC5025.8μMforCOX-2).Followingoraladministrationofthedrug,maximalexvivoinhibitionsare56%(COX-1)and83%(COX-2).AcetaminophenplasmaconcentrationsremaineabovetheinvitroIC50forCOX-2foratleast5hpostadministration.ExvivoIC50values(COX-1:105.2μM;COX-2:26.3μM)ofacetaminophencomparedfavorablywithitsinvitroIC50values.Incontrasttopreviousconcepts,acetaminopheninhibitedCOX-2bymorethan80%,i.e.,toadegreecomparabletononsteroidalantiinflammatorydrugs(NSAIDs)andselectiveCOX-2inhibitors.However,a>95%COX-1blockaderelevantforsuppressionofplateletfunctionisnotachieved[1].MTTassayshowsthatAcetaminophen(APAP)inadoseof50mMsignificantly(p<0.001)reducescellviabilityto61.5±6.65%.Interestingly,thesignificant(p<0.01)increaseincellviabilityto79.7±2.47%isobservedintheAcetaminophen/HV110co-treatedcells,comparedtoAcetaminophentreatedcells[2].体内研究AdministeringAcetaminophen(250mg/kg,orally)tothemicecausessignificant(p<0.001)liverdamageandnecrosisofcellsasevidencedbytheelevatedserumhepaticenzymesalanineaminotransferase(ALT),aminotransferase(AST),alkalinephosphatase(ALP),andgamma-glutamyltransferase(γGT)comparedwithnormalgroup.Conversely,effects

ofpretreatmentwithdifferentdosesofcitral(125,250,and500mg/kg)exhibitedasignificant(p<0.05)decreasein

serumactivitiesofALT(91.79%,93.07%,and95.61%,resp.),AST(93.40%,91.89%,and96.52%,resp.),ALP(39.29%,37.07%,and59.80%,resp.),andγGT(92.83%,91.59%,and93.0%,resp.),whencomparedtotheAcetaminophen

group.SimilarresultswerefoundinpretreatmentwithSLMontheactivityofALT(95.90%),AST(95.03%),ALP

(70.52%),andγGT(92.69%)[3].PROTOCOLCellAssay[2]HumanhepatomacelllineHepG2isculturedinlowglucoseDMEMsupplementedwith10%fetalbovineserum(FBS),100U/mLPenicillinand100μg/mLStreptomycinand2mMl-glutamine.Thecellsaremaintainedin75cm2flasksat37°Cinahumidifiedatmospherecontaining5%CO2andsplitat80%confluenceevery5days.Cellsareseededin24-wellplate(2×105cells)andincubatedat37°CovernightfollowedbycellspretreatmentwithcompleteDMEMcontaininghighglucoseconcentrationinordertodownregulateautophagy.After6h,cellsaretreatedwithdifferentconcentrationsofpostbioticsobtainedfromLactobacillusfermentumBGHV110strain(HV110)inordertoselectappropriatedoseforfurtherexperiments.PostbioticisdissolvedincompleteDMEMmediumandaddedtothecellsinspecificfinalconcentration.Inallotherexperimentsseededcellsaretreatedwith50mMAcetaminophenaloneorco-treatedwith50mMAcetaminophenandselecteddoseoflyophilizedHV110.Toanalyzeautophagicflux,Page2of3www.MedChemEsimultaneouslywithtreatments,cellsareexposedtolysosomotropicagentChloroquineataconcentrationof25μM,toinhibitautophagosome-lysosomefusion[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]MaleSwissmice(30-40g)areused.Theexperimentalanimalsaredividedintosixgroupsoffiveanimalseach.Firstly,eachgroupreceiveorallyduringsevendaysthefollowingtreatment:GroupI:themicedonotreceiveanytreatment(normal).GroupII:themicereceivecitralvehicle(0.1%Tween80solution).GroupsIII-V:themicearepretreatedwithcitralatdosesof125,250,and500mg/kg,respectively.GroupVI:themicearepretreatedwiththehepatoprotectivestandarddrugSilymarin(SLM)(200mg/kg).Afterthistime,theanimalsfastedfor8handthenreceiveoralAcetaminophenontheseventhdayatadoseof250mg/kginGroupsII-VI.GroupIorallyreceivesalinethatcontained0.1%Tween80solution(Acetaminophenvehicle).Thestocksolutionisusedasthefirstconcentrationof50mg/mLandafterthatisdilutedin0.1%Tween80solutiontopreparethesolutionsof25and12.5mg/mL.After12hofAcetaminophenadministration,serumsamplesandlivertissuearecollectedfollowedbybiochemistryandhistologicalanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Theranostics.2017Sep26;7(17):4135-4148.•LabChip.2018Nov6;18(22):3379-3392.•Chemosphere.2019Jun;225:378-387.•JCellPhysiol.2020Apr;235(4):3329-3339.•BioorgChem.2020Jan30;96:103630.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Hinz,B,etal.Acetaminophen(paracetamol)isaselectivecyclooxygenase-2inhibitorinman.FASEBJ,2008.