Rosiglitazone-maleate-BRL-49653C-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERosiglitazonemaleateCat.No.:HY-14600CASNo.:155141-29-0Synonyms:BRL49653C分⼦式:C₂₂H₂₃N₃O₇S分⼦量:473.5作⽤靶点:PPAR;TRPChannel;Autophagy;Autophagy;Ferroptosis作⽤通路:CellCycle/DNADamage;MembraneTransporter/IonChannel;NeuronalSignaling;Autophagy;Apoptosis储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:100mg/mL(211.19mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic)(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1119mL10.5597mL21.1193mL5mM0.4224mL2.1119mL4.2239mL10mM0.2112mL1.0560mL2.1119mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.28mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.28mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.28mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Rosiglitazonemaleate(BRL49653C)⼀种有效的，选择性的PPARγ激活剂，对PPARγ1，PPARγ2和PPARγ的EC50值分别为30nM，100nM和60nM，对PPARγ的Kd值约为40nM；Rosiglitazonemaleate同时为TRPchannels的调节剂，可抑制TRPM2,TRPM3的活性，激活TRPC5[1]。IC50&TargetPPARγ1PPARγ230nM(EC50)100nM(EC50)体外研究RosiglitazonemaleateisapotentandselectiveactivatorofPPARγ,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].体内研究Rosiglitazone(5mg/kg,p.o.)decreasestheserumglucoseindiabeticrats.RosiglitazonealsodecreasesIL-6,TNF-α,andVCAM-1levelsindiabeticgroup.RosiglitazoneincombinationwithlosartanincreasesglucosecomparedtodiabeticandLos-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].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.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.户使⽤本产品发表的科研⽂献•Circulation.2022Nov30.•CellMetab.2021Mar2;33(3):581-597.e9.•JExpMed.2022May2;219(5):e20211906.•CancerRes.2022Apr15;82(8):1503-1517.•CellDeathDiffer.2022Nov3.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LehmannJM,etal.Anantidiabeticthiazolidinedioneisahighaffinityligandforperoxisomeproliferator-activatedreceptorgamma(PPARgamma).JBiolChem.1995Jun2;270(22):12953-6.[2].WillsonTM,etal.Thestructure-activityrelationshipbetweenperoxisomeproliferator-activatedreceptorgammaagonismandtheantihyperglycemicactivityofthiazolidinediones.JMedChem.1996Feb2;39(3):665-8.[3].ThouennonE,etal.Rosiglitazone-acti