YM-244769-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEYM-244769Cat.No.:HY-136182ACASNo.:838819-70-8分⼦式:C₂₆H₂₂FN₃O₃分⼦量:443.47作⽤靶点:Na+/Ca2+Exchanger作⽤通路:MembraneTransporter/IonChannel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:120mg/mL(270.59mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2549mL11.2747mL22.5494mL5mM0.4510mL2.2549mL4.5099mL10mM0.2255mL1.1275mL2.2549mL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.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.69mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性YM-244769⼀种有效的、选择性的、具有⼝服活性的Na+/Ca2+交换体(NCX)抑制剂。YM-244769优先抑制NCX3，抑制NCX单向向外电流(Ca2+进⼊模式)，IC50值分别为18nM和50nM。YM-244769可有效预防缺氧/复氧诱导的SH-SY5Y神经元细胞损伤。YM-244769还能增加⼩⿏的尿量和尿液中电解质的排泄。IC50&TargetIC50:18nM(NCX3),68nM(NCX1),96nM(NCX2)[1]体外研究YM-244769(0.003-1μM)inhibitsdosedependentlytheinitialratesof45Ca2+uptakeintoNCX1,NCX2,andNCX3transfectantswithIC50valuesof68±2.9,96±3.5,and18±1.0nM,respectively[1].YM-244769(0.3or1μM)efficientlyprotectsagainstthehypoxia/reoxygenation-inducedlactatedehydrogenase(LDH)releaseinSH-SY5YcellsandinLLC-PK1cells(1μM)[1].YM-244769possessesreversemode-selectivity[1].YM-244769(1and10μM)inhibitsNCXcurrent(INCX)inaconcentration-and[Na+]i-dependentmanner,theIC50againsttheunidirectionaloutwardINCX(Ca2+entrymode)is0.05μM.TheIC50valuesagainstthebidirectionaloutwardandinwardINCXaresimilarandapproximately100nMwithaHillcoefficientofabout1[3].YM-244769istrypsin-insensitive[3].CellViabilityAssay[1]CellLine:SH-SY5YcellstreatedwithNCX1orNCX3antisenseConcentration:0.3and1μMIncubationTime:Result:Hypoxia/reoxygenation-inducedLDHreleasewassignificantlyattenuated:reductionincelldamagewasgreaterincellstreatedwithNCX3antisense(by61%)thanincellstreatedwithNCX1antisense(by35%).0.3or1μMefficientlysuppressedthehypoxia/reoxygenation-inducedcelldamageinSH-SY5YcellstreatedwithNCX1antisensemorethaninthosetreatedwithNCX3antisense.体内研究YM-244769(0.1-1mg/kg;p.o.;once)exhibitsdose-dependentlynatriureticactioninmiceandsignificantlyincreasesurinaryexcretionofCa2+aswellasCa2+/Crratio[2].AnimalModel:Wild-typeC57BL/6JmiceandNCX-KOmice[2]Dosage:0.1,0.3and1mg/kgAdministration:Oraladministration,onceResult:Causedadose-dependentincrease(uptoapproximately200%)inurinevolumeandurinaryexcretionofelectrolytes(Na+,K+andCl-).NatriureticactionswereequivalentlyobservedinNCX1-KOandWT,butdisappearedinNCX2-KOanddoubleKO.REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].IwamotoT,KitaS.YM-244769,anovelNa+/Ca2+exchangeinhibitorthatpreferentiallyinhibitsNCX3,efficientlyprotectsagainsthypoxia/reoxygenation-inducedSH-SY5Yneuronalcelldamage.MolPharmacol.2006Dec;70(6):2075-83.[2].GotohY,etal.GeneticknockoutandpharmacologicinhibitionofNCX2causenatriuresisandhypercalciuria.BiochemBiophysResCommun.2015Jan9;456(2):670-5.[3].YamashitaK,etal.InhibitoryeffectofYM-244769,anovelNa+/Ca2+exchangerinhibitoronNa+/Ca2+exchangecurrentinguineapigcardiacventricularmyocytes.NaunynSchmiedebergsArchPharmacol.2016Nov;389(11):1205-1214.McePdfHeightCauti