AMG-337-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAMG-337Cat.No.:HY-18696CASNo.:1173699-31-4分⼦式:C₂₃H₂₂FN₇O₃分⼦量:463.46作⽤靶点:c-Met/HGFR;Caspase;Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(215.77mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1577mL10.7884mL21.5768mL5mM0.4315mL2.1577mL4.3154mL10mM0.2158mL1.0788mL2.1577mL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(5.39mM);Clearsolution1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.39mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.39mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AMG-337⼀种⼝服有效的选择性MET激酶抑制剂，抑制WTMET、H1094RMET、M1250TMET、HGF-stimulatedpMET(PC3细胞)MET、V1092IMET、Y1230HMET和D1228HMET的IC50值分别为1、1、4.7、5、21.5、1077和>4000nM。AMG337在MET扩增的癌细胞系中抑制MET及其下游效应⼦的磷酸化，从⽽抑制MET依赖的细胞增殖和诱导凋亡(apoptosis)。IC50&TargetIC50:1(WTMET),1(H1094RMET),4.7(M1250TMET),5(HGF-stimulatedpMET(PC3cells)MET),21.5(V1092IMET),1077(Y1230HMET)and>4000nM(D1228HMET)[1]体外研究AMG337(0-3µM;72h)inhibitsproliferationinMET-dependentcancercelllines[1].AMG337(0-300nM;0-24h;MKN-45,SNU-620,andSNU-5cells)inhibitssignalingthroughthePI3KandMAPKpathwaysinMET-amplifiedgastriccancercelllines,resultinginaninhibitionofMET-dependentcellproliferationandinductionofapoptosis[1].ApoptosisAnalysis[1]CellLine:MKN-45andSNU-620cellsConcentration:0,3,10,30,100and300nMIncubationTime:24hoursResult:Increasedthenumberofcellsundergoingapoptosis.CellCycleAnalysis[1]CellLine:MKN-45andSNU-620cellsConcentration:0,3,10,30,100and300nMIncubationTime:24hoursResult:Increasedinadose-dependentincellsintheG1phaseandwithconcurrentreductionofcellsinS-phase.WesternBlotAnalysis[1]CellLine:MKN-45,SNU-620,andSNU-5cellsConcentration:100nM2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:2hoursResult:InhibitedMETphosphorylationandphosphorylationofdownstreameffectors.WesternBlotAnalysis[1]CellLine:MKN-45,SNU-620,andSNU-5cellsConcentration:100nMIncubationTime:24hoursResult:InducedPARPandcaspase-3cleavageinSNU-620andSNU-5cells.体内研究AMG337(0-30mg/kg;p.o.;daily,for28d)inhibitsMETsignalingintumorxenograftsandinhibitstumorgrowthinMET-dependenttumorxenograftmodels[1].AMG337(0-3mg/kg;p.o.;once,for3or24h)isassociatedwithincreasednecrosisintheMET-dependentSNU-620tumorxenograftmodel[1].AnimalModel:FemaleCD1nu/numicebearingSNU-620,SNU-5,orU-87MGxenografts[1]Dosage:0,0.3,and1mg/kg(SNU-620xenograft);0,0.3,1,3,and10mg/kg(SNU-5xenograft);0,3,10and30mg/kg(U-87xenograft)Administration:Oraladministration;daily,for28daysResult:InhibitedtumorgrowthinMET-dependenttumorxenograftmodels.AnimalModel:FemaleCD1nu/numicebearingSNU-620,SNU-5,orU-87MGxenografts[1]Dosage:0.1,0.5,0.75,1,2,and3mg/kgAdministration:Oraladministration;once,for3hoursResult:InhibitedGab-1phosphorylationinadose-dependentmanner.AnimalModel:FemaleCD1nu/numicewithSNU-620xenograftmodel(6-11weeksofage;20-26g)[1]Dosage:0,0.3,1,and3mg/kgAdministration:Oraladministration;once,for3or24hoursResult:Increasedimmunohistochemicalstainingwithanti-caspase-3antibodyanddecreasedimmunohistochemicalstainingwithanti-BrdUantibody.REFERENCES3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].HughesPE,et,al.InVitroandInVivoActivityofAMG337,aPotentandSelectiveMETKinaseInhibitor,inMET-DependentCancerModels.MolCancerTher.2016Jul;15(7):1568-79.[2].DuZ,et,al.PreclinicalEvaluationofAMG337,aHighlySelectiveSmallMoleculeMETInhibitor,inHepatocellularCarcinoma.MolCancerTher.2016Jun;