Rosiglitazone-maleate-BRL-49653C-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERosiglitazonemaleateCat.No.:HY-14600CASNo.:155141-29-0Synonyms:BRL49653C分?式:C??H??N?O?S分?量:473.5作?靶點(diǎn):PPAR;TRPChannel;Autophagy;Autophagy;Ferroptosis作?通路:CellCycle/DNADamage;MembraneTransporter/IonChannel;NeuronalSignaling;Autophagy;Apoptosis儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(211.19mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.1119mL10.5597mL21.1193mL5mM0.4224mL2.1119mL4.2239mL10mM0.2112mL1.0560mL2.1119mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.28mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.28mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.28mM);ClearsolutionBIOLOGICALACTIVITY?物活性Rosiglitazonemaleate(BRL49653C)?種有效的，選擇性的PPARγ激活劑，對(duì)PPARγ1，PPARγ2和PPARγ的EC50值分別為30nM，100nM和60nM，對(duì)PPARγ的Kd值約為40nM；Rosiglitazonemaleate同時(shí)為T(mén)RPchannels的調(diào)節(jié)劑，可抑制TRPM2,TRPM3的活性，激活TRPC5[1]。IC50&TargetPPARγ1PPARγ230nM(EC50)100nM(EC50)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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