Rosiglitazone-sodium-BRL-49653-sodium-生命科學試劑-MCE

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERosiglitazonesodiumCat.No.:HY-B0700CASNo.:316371-83-2Synonyms:BRL49653sodium分?式:C??H??N?NaO?S分?量:379.41作?靶點:PPAR;TRPChannel;Autophagy作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Vitamin

DRelated/NuclearReceptor;MembraneTransporter/Ion

Channel;NeuronalSignaling;Autophagy儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Rosiglitazonesodium?種有效的，選擇性的PPARγ激活劑，對PPARγ1，PPARγ2和PPARγ的EC50值分別為30nM，100nM和60nM，對PPARγ的Kd值約為40nM；Rosiglitazonesodium同時為TRPchannels的調(diào)節(jié)劑，可抑制TRPM2,TRPM3的活性，激活TRPC5的活性。IC50&TargetPPARγ1PPARγ230nM(EC50)100nM(EC50)體外研究RosiglitazonesodiumisapotentandselectiveactivatorofPPARγ,withEC50sof30nMand100nMforPPARγ1andPPARγ2,respectively,andaKdofappr40nMforPPARγ.Rosiglitazone(BRL49653,0.1,1,10μM)promotesdifferentiationofC3H10T1/2stemcellstoadipocytes[1].Rosiglitazone(Compound6)activatesPPARγ,withanEC50of60nM[2].Rosiglitazone(1μM)activatesPPARγ,whichbindstoNF-α1promotertoactivategenetranscriptioninneurons.Rosiglitazone(1μM)alsoprotectsNeuro2Acellsandhippocampalneuronsagainstoxidativestress,andup-regulatesBCL-2expressioninanNF-α1-dependentmanner[3].RosiglitazonecompletelyinhibitsTRPM3withIC50valuesof9.5and4.6μMagainstnifedipine-andPregS-evokedactivity,butsucheffectsarenotviaPPARγ.RosiglitazoneinhibitsTRPM2athigherconcentration,withanIC50ofappr22.5μM.RosiglitazoneisastrongstimulatorofTRPC5channels,withanEC50of-30μM[4].體內(nèi)研究Rosiglitazone(5mg/kg,p.o.)decreasestheserumglucoseindiabeticrats.RosiglitazonealsodecreasesIL-6,TNF-α,andVCAM-1levelsindiabeticgroup.Rosiglitazoneincombinationwithlosartanincreasesglucose1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEcomparedtodiabeticandLos-treatedgroups.RosiglitazonesignificantlyamelioratesendothelialdysfunctionindicatedbyasignificantlylowercontractileresponsetoPEandAngIIandenhancementofACh-provokedrelaxationinaortasisolatedfromdiabeticrats[5].PROTOCOLKinaseAssay[1]cDNAencodingaminoacids174-475ofPPARγ1isamplifiedviapolymerasechainreactionandinsertedintobacterialexpressionvectorpGEX-2T.GST-PPARγLBDisexpressedinBL21(DE3)plysScellsandextracts.Forsaturationbindinganalysis,bacterialextracts(100μgofprotein)areincubatedat4°Cfor3hinbuffercontaining10mMTris(pH8.0),50mMKCl,10mMdithiothreitolwith[3H]-BRL49653(specificactivity,40Ci/mmol)inthepresenceorabsenceofunlabeledRosiglitazone.Boundisseparatedfromfreeradioactivitybyelutionthrough1-mLSephadexG-25desaltingcolumns.Boundradioactivityelutedinthecolumnvoidvolumeandisquantitatedbyliquidscintillationcounting[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]C3H10T1/2cellsaregrownina24-wellplateinDMEmediumsupplementedwith10%fetalcalfserum.Mediumandcompound(Rosiglitazone)areexchangedevery3days.Cellsarestainedatday7withOilRedOandphotographed[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRatsareintravenouslyinjectedwith38mg/kgstreptozotocinandafter48h,diabetesisidentifiedbyurinaryAdministration[2]glucosuriaandthenrandombloodsugarismeasuredandthisdayisregardedasday0.Animalswithaserumglucoselevelof220-300mg/dLareselectedtobeusedinthisstudy.Ratsarerandomlyseparatedintofivegroupsfordailydrugadministrationfor8weeks:group1:controlnondiabeticratsgivenavehicleonly(0.5mL/kgof0.5%carboxymethylcelleluseorally),group2:controldiabeticratsgivenavehicle,group3:diabeticratsreceivingRosiglitazone(5mg/kgorally),group4:diabeticratsreceivinglosartan(2mg/kg,orally),andgroup5:diabeticratsreceivingbothRosiglitazoneandlosartan[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CancerCell.2024May13;42(5):869-884.e9.?Circulation.2022Nov30.?CellMetab.2023Dec5;35(12):2165-2182.e7.?CellMetab.2023Sep7;S1550-4131(23)00304-2.?CellMetab.2021Mar2;33(3):581-597.e9.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LehmannJM,etal.Anantidiabeticthiazolidinedioneisahighaffinityligandforperoxisomeproliferator-activatedreceptorgamma(PPAR2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEgamma).JBiolChem.1995Jun2;270(22):12953-6.[2].WillsonTM,etal.Thestructure-activityrelationshipbetweenperoxisomeproliferator-activatedreceptorgammaagonismandtheantihyperglycemicactivityofthiazolidinediones.JMedChem.1996Feb2;39(3):665-8.[3].ThouennonE,etal.Rosiglitazone-activatedPPARγinducesneurotrophicfactor-α1transcriptioncontributingtoneuroprotection.JNeurochem.2015Aug;134(3):463-70.[4].MajeedY,etal.RapidandcontrastingeffectsofrosiglitazoneontransientreceptorpotentialTRPM3andTRPC5channels.MolPharmacol.2011Jun;79(6):1023-30.[5].AteyyaH,etal.Beneficialeffectsofrosiglitazoneandlosartancombinationin