NCGC00378430-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENCGC00378430Cat.No.:HY-138657CASNo.:920650-00-6分⼦式:C₂₂H₂₃N₃O₅S分⼦量:441.5作⽤靶点:Phosphatase作⽤通路:MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(226.50mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2650mL11.3250mL22.6501mL5mM0.4530mL2.2650mL4.5300mL10mM0.2265mL1.1325mL2.2650mL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。-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>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.66mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.66mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性NCGC00378430⼀种有效的SIX1/EYA2相互作⽤抑制剂。NCGC00378430部分逆转SIX1过表达介导的转录和代谢谱，并逆转SIX1诱导的TGF-β信号传导和上⽪-间质转化(EMT)。NCGC00378430在⼩⿏模型中抑制SIX1介导的乳腺癌转移。体外研究NCGC00378430isapotentSIX1/EYA2interactioninhibitorwithanIC50of52μMintheAlphascreenassay[1].NCGC00378430(20μM;3days)blocksTGF-βinducedactivationofp-Smad3,upregulationofFN1,anddownregulationofE-CADinT47Dcells[1].NCGC00378430(10μM;3days)reversestheSineoculishomeoboxhomolog1(SIX1)-inducedincreaseinp-SMAD3anddoesnotaltertotalE-CADlevels.NCGC00378430restoresmembranousE-CADinMCF7-SIX1cells,alongwithinhibitingFN1expression[1].NCGC00378430(10or20μM)disruptsSIX1-EYA2interactioninbreastcancercells(MCF7,T47D,MDA-MB-231cells)[1].NCGC00378430(10μM;for3days)partiallyreversesSIX1-mediatedtranscriptionalandmetabolicsignaturesinMCF7breasttumorcells[1].WesternBlotAnalysis[1]CellLine:T47DcellsConcentration:20μMIncubationTime:3daysResult:BlockedTGF-βinducedactivationofp-Smad3,upregulationofFN1,anddownregulationofE-CAD.体内研究NCGC00378430(25mg/kg;localinjectiontothesiteoftumor;everyotherday;fromday3untiltheday21)dramaticallydecreasesdistantmetastaticburdencomparedtovehicletreatment[1].NCGC00378430(20mg/kg;IV)hasaT1/2αof0.25hours[1].AnimalModel:6-8weekoldNSGmicewithMCF7tumorcells[1]Dosage:25mg/kgAdministration:LocalInjectiontothesiteoftumor;everyotherday;fromday3untiltheday21Result:Dramaticallydecreaseddistantmetastaticburdencomparedtovehicletreatment.Hadnogrowthinhibitoryeffect.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:Mice[1]Dosage:20mg/kg(PharmacokineticAnalysis)Administration:IVResult:HadaT1/2αof0.25hours,aCLof6.19L/hr•kg,aVssof4.08L/kg,aCmaxof6703ng/mLandanAUCof3234ng/mL•hr.REFERENCES[1].HengboZhou,etal.IdentificationofaSmall-MoleculeInhibitorThatDisruptstheSIX1/EYA2Complex,EMT,andMetastasis.CancerRes.2020Jun15;80(12):2689-2702.McePdfHeightCaution:Producthasnotbeenfullyvali