BMS-687453-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBMS-687453Cat.No.:HY-10678CASNo.:1000998-59-3分?式:C??H??ClN?O?分?量:444.86作?靶點:PPAR作?通路:CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥100mg/mL(224.79mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2479mL11.2395mL22.4790mL5mM0.4496mL2.2479mL4.4958mL10mM0.2248mL1.1239mL2.2479mL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；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.62mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.62mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性BMS-687453?種有效的，選擇性的PPARα激動劑，對?PPARα的EC50和IC50分別為10nM和260nM；較弱地抑制PPARγ的活性，EC50和IC50值分別為4100nM和>15000nM。IC50&TargetPPARα260nM(IC50,HumanPPARα)體外研究BMS-687453isapotentandselectivePPARαagonist,withanEC50andIC50of10nMand260nMforhumanPPARαand-410-foldandmorethan57-foldselectivityvshumanPPARγof4100nMand>15000nMinPPAR-GAL4transactivationassays.BMS-687453exhibitshighPPARαpotency(EC50=47nM)with-50-foldselectivityvsPPARγ(EC50=2400nM)inHepG2cells.However,BMS-687453showslesspotentactivitiesinrodentPPARαfunctionalassays,withamoderateEC50of426nMformouseand488nMforhamsterbutremainsafullPPARαagonistinbothspecies[1].體內(nèi)研究BMS-687453(10,50,100,p.o.)dose-dependentlyincreasesserumApoA1proteinlevelsandlow-densitylipoprotein-cholesterol(LDLc)levelsinmice.BMS-687453(1,3,10mg/kg,p.o.)decreasesHDLclevelsinhighfat-fedhamsters[1].BMS-687453inducesPDK4mRNAintheliver,withED50valueof0.24mg/kg[2].BMS-687453(300mg/kg,p.o.)causesskeletalmyofiberdegenerationandnecrosischaracterizedbyobserveddiscoidchanges,myofibrillysis,hyalinization,andcellularinfiltrationinmalerats.BMS-687453(300mg/kg,p.o.)inducesamildtoxicityinbothfastandslow-twitchmusclesinmalerats[3].PROTOCOLKinaseAssay[1]Ahomogeneous,fluorescentpolarizationPPARαandPPARγbindingassayisusedastheprimaryscreenfordeterminingthePPARαandPPARγbindingaffinityofcompounds.ThehumanfunctionalactivityofPPARαandPPARγagonistsisdeterminedbyusingtheGAL4-LBDassays.Theinvitrohamster,rat,andmousePPARαfunctionalactivitiesaretestedinthechimericGAL4/PPARαassayformat.ThedataarereportedasanEC50valuecalculatedusingXLfit4parameterfitandfloatingallparameters.FulllengthhumanPPARαandPPARγco-transfectionassaysinHepG2cellsareemployedforfurthertestingtheleadingcompounds(BMS-687453)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMale6?8weekoldhumanapoA1transgenicmicearerandomlyassignedintodifferenttreatmentgroupsandAdministration[1]weighedanddosedbyoralgavage(5mL/kgbodyweight)onceadayinthemorningwithvehiclealoneorwithcompound(BMS-687453)andallowedfreeaccesstofoodandwater.Thestudydurationis10days.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAfterdosingonday10,micearefastedfor4handsacrificedbyCO2asphyxiation,andbloodsamplesarecollectedinserum-separatingtubesviacardiacpunctureforlipidmeasurements.Liversaredissectedout,weighed,andquicklyfrozeninliquidnitrogenforfutureRNAanalysis.HumanapoA1concentrationinserumismeasuredusingtheapolipoproteinA1kit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?RadboudUniversityNijmegen.2021Mar.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiJ,etal.Discoveryofanoxybenzylglycinebasedperoxisomeproliferatoractivatedreceptoralphaselectiveagonist2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)aceticacid(BMS-687453).JMedChem.2010Apr8;53[2].MukherjeeR,etal.Novelperoxisomeproliferator-activatedreceptoralphaagonistslowerlow-densitylipoproteinandtriglycerides,raisehigh-densitylipoprotein,andsynergisticallyincreasecholesterolexcretionwithaliverXreceptoragonist.JPhar[3].VassalloJD,etal.Biomarkersofdrug-inducedskeletalmuscleinjuryintherat:troponinIandmyoglobi