Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAcetaminophenCat.No.:HY-66005CASNo.:103-90-2Synonyms:Paracetamol;4-Acetamidophenol;4'-Hydroxyacetanilide分?式:C?H?NO?分?量:151.16作?靶點:COX;HistoneAcetyltransferase;EndogenousMetabolite;Bacterial;Parasite作?通路:Immunology/Inflammation;Epigenetics;MetabolicEnzyme/Protease;Anti-infection儲存?式:Powder-20°C3years4°C2years*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(1653.88mM;Needultrasonic)H2O:10mg/mL(66.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM6.6155mL33.0775mL66.1551mL5mM1.3231mL6.6155mL13.2310mL10mM0.6616mL3.3078mL6.6155mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：0.5%CMC-Na/salinewaterSolubility:10mg/mL(66.16mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(13.76mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(13.76mM);Clearsolution4.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(13.76mM);Clearsolution5.請依序添加每種溶劑：PBSSolubility:6.67mg/mL(44.13mM);Clearsolution;Needultrasonic6.請依序添加每種溶劑：saline>>0.5%Tween-80Solubility:10mg/mL(66.16mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Acetaminophen(Paracetamol)選擇性環(huán)氧合酶-2(COX-2)的抑制劑，IC50值為25.8μM。Acetaminophen?種有效的肝N-?酰轉(zhuǎn)移酶2(NAT2)抑制劑。Acetaminophen?泛使?的解熱和?痛劑[1][2][3][4]。IC50&TargetCOX-2COX-125.8μM(IC50)113.7μM(IC50)體外研究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[2].體內(nèi)研究AdministeringAcetaminophen(250?mg/kg,orally)tothemicecausessignificant(p[3].PROTOCOLCellAssay[2]HumanhepatomacelllineHepG2isculturedinlowglucoseDMEMsupplementedwith10%fetalbovineserum(FBS),100U/mLPenicillinand100μg/mLStreptomycinand2mMl-glutamine.Thecellsaremaintainedin75cm2flasksat37°Cinahumidifiedatmospherecontaining5%CO2andsplitat80%confluenceevery5days.Cellsareseededin24-wellplate(2×105cells)andincubatedat37°CovernightfollowedbycellspretreatmentwithcompleteDMEMcontaininghighglucoseconcentrationinordertodownregulateautophagy.After6h,cellsaretreatedwithdifferentconcentrationsofpostbioticsobtainedfromLactobacillusfermentumBGHV110strain(HV110)inordertoselectappropriatedoseforfurther2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEexperiments.PostbioticisdissolvedincompleteDMEMmediumandaddedtothecellsinspecificfinalconcentration.Inallotherexperimentsseededcellsaretreatedwith50mMAcetaminophenaloneorco-treatedwith50mMAcetaminophenandselecteddoseoflyophilizedHV110.Toanalyzeautophagicflux,simultaneouslywithtreatments,cellsareexposedtolysosomotropicagentChloroquineataconcentrationof25μM,toinhibitautophagosome-lysosomefusion[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]MaleSwissmice(30-40?g)areused.Theexperimentalanimalsaredividedintosixgroupsoffiveanimalseach.Firstly,eachgroupreceiveorallyduringsevendaysthefollowingtreatment:GroupI:themicedonotreceiveanytreatment(normal).GroupII:themicereceivecitralvehicle(0.1%Tween80solution).GroupsIII-V:themicearepretreatedwithcitralatdosesof125,250,and500?mg/kg,respectively.GroupVI:themicearepretreatedwiththehepatoprotectivestandarddrugSilymarin(SLM)(200?mg/kg).Afterthistime,theanimalsfastedfor8?handthenreceiveoralAcetaminophenontheseventhdayatadoseof250?mg/kginGroupsII-VI.GroupIorallyreceivesalinethatcontained0.1%Tween80solution(Acetaminophenvehicle).Thestocksolutionisusedasthefirstconcentrationof50?mg/mLandafterthatisdilutedin0.1%Tween80solutiontopreparethesolutionsof25and12.5?mg/mL.After12?hofAcetaminophenadministration,serumsamplesandlivertissuearecollectedfollowedbybiochemistryandhistologicalanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?NatCommun.2021Sep20;12(1):5548.?NatCommun.2021Aug26;12(1):5131.?NatCommun.2021May17;12(1):2863.?Hepatology.2022Jun17.?Theranostics.2017Sep26;7(17):4135-4148.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Hinz,B,etal.Acetaminophen(paracetamol)isaselectivecyclooxygenase-2inhibitorinman.FASEBJ,2008.22(2):p.383-90.[2].MiroslavDini?,etal.LactobacillusfermentumPostbiotic-inducedA