A-192621-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEA-192621Cat.No.:HY-120295CASNo.:195529-54-5分?式:C??H??N?O?分?量:558.66作?靶點:EndothelinReceptor;Apoptosis作?通路:GPCR/GProtein;Apoptosis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(179.00mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7900mL8.9500mL17.9000mL5mM0.3580mL1.7900mL3.5800mL10mM0.1790mL0.8950mL1.7900mL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(fù)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(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.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(4.47mM);ClearsolutionBIOLOGICALACTIVITY?物活性A-192621?種有效的?肽，?服活性，選擇性內(nèi)?素B(ETB)受體拮抗劑，IC50為4.5nM，Ki為8.8nM。A-192621的選擇性?ETA?636倍(IC50為4280nM，Ki為5600nM)。A-192621促進PASMC細胞凋亡，并引起動脈?壓升?和?漿ET-1?平升?。IC50&TargetETBETBETAETA4.5nM(IC50)8.8nM(Ki)4280nM(IC50)5600nM(Ki)體外研究A-192621(1-100μM;48hours;PASMCs)treatmentmarkedlyreducesthecellviabilityofPASMCsinadose-dependentmanner[2].A-192621(1-100μM;48hours;PASMCs)treatmentsignificantlyincreasesthecaspase-3/7activityandcleavedcaspase-3expressioninPASMCs.A-192621inducesapoptosisinadose-dependentmannerandincreasesthecells'susceptibilitytoapoptosisbyDoxorubicintreatment[2].CellViabilityAssay[2]CellLine:Pulmonaryarterialsmoothmusclecells(PASMCs)withDoxorubicinConcentration:1μM,10μM,50μM,100μMIncubationTime:72hoursResult:TheviabilityofPASMCswassignificantlydecreasedinadose-dependentmanner.WesternBlotAnalysis[2]CellLine:Pulmonaryarterialsmoothmusclecells(PASMCs)withDoxorubicinConcentration:1μM,10μM,100μMIncubationTime:72hoursResult:Thecaspase-3/7activityinPASMCswassignificantlyincreasedinadose-dependentmanner.體內(nèi)研究A-192621(30-100mg/kg;oraladministration;daily;for3days;maleSprague-Dawleyrats)treatmentinhibitsbothdilatoryandpressorresponsesinducedbyS6cmediatedbyETBwithanED50valueof30mg/kg,andfailedtoinhibittheET-1-inducedpressorresponsemediatedbyETA.A-192621alonecauseselevationofarterialbloodpressureandanelevationintheplasmaET-1levelintheconsciousnormotensiverat[3].AnimalModel:MaleSprague-Dawleyrats(250-350g)[3]Dosage:30mg/kg100mg/kg2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:Oraladministration;daily;for3daysResult:InhibitedbothdilatoryandpressorresponsesinducedbyS6cmediatedbyETBwithanED50valueof30mg/kg.REFERENCES[1].Wu-WongJR,etal.PharmacologyofendothelinreceptorantagonistsABT-627,ABT-546,A-182086andA-192621:invitrostudies.ClinSci(Lond).2002Aug;103Suppl48:107S-111S.[2].SakaiS,etal.AntagoniststoendothelinreceptortypeBpromoteapoptosisinhumanpulmonaryarterialsmoothmusclecells.LifeSci.2016Aug15;159:116-120.[3].WessaleJL,etal.PharmacologyofendothelinreceptorantagonistsABT-627,ABT-546,A-182086andA-192621:exvivoandinvivostudies.ClinSci(Lond).2002Aug;103Suppl48:112S-117S.McePdfHeightCaution:Producthasnot