Lenvatinib-E7080-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELenvatinibCat.No.:HY-10981CASNo.:417716-92-8Synonyms:E7080分⼦式:C₂₁H₁₉ClN₄O₄分⼦量:426.85作⽤靶点:VEGFR;FGFR;PDGFR;c-Kit;RET作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥12.78mg/mL(29.94mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3427mL11.7137mL23.4274mL5mM0.4685mL2.3427mL4.6855mL10mM0.2343mL1.1714mL2.3427mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：0.5%Methylcellulose/salinewaterSolubility:6.67mg/mL(15.63mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥0.64mg/mL(1.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Lenvatinib(E7080)⼀种具有⼝服活性的，多靶点酪氨酸激酶抑制剂，抑制⾎管内⽪⽣长因⼦受体(VEGFR1-3)，成纤维细胞⽣长因⼦受体(FGFR1-4)，⾎⼩板衍⽣⽣长因⼦受体(PDGFR)，⼲细胞因⼦受体(KIT)，转染期间重排(RET)，显⽰有效抗癌的活性[1][2]。IC50&TargetVEGFR2VEGFR3VEGFR1FGFR14nM(IC50)5.2nM(IC50)22nM(IC50)46nM(IC50)FGFR2FGFR3FGFR4PDGFRα51nM(IC50)PDGFRβc-KitRET39nM(IC50)100nM(IC50)体外研究Lenvatinib(E7080)hasIC50sof4,5.2,22nMforVEGFR2(KDR),VEGFR3(Flt-4),andVEGFR1(Flt-1),respectively.LenvatinibinhibitsPDGFRα,PDGFRβ,FGFR1,andKITwithIC50sof51,39,46,and100nM,respectively[3].体内研究Lenvatinib(E7080)(100mg/kg,p.o.)significantlyinhibitslocaltumorgrowthatthem.f.p.,andattheendoftreatment,Lenvatinibmesylatealsosignificantlyinhibitsmetastasistobothregionallymphnodesanddistantlung[3].Lenvatinib(E7080)inhibitsthegrowthofH146tumorat30and100mg/kg(BID,QDx21)inadose-dependentmannerandcausestumorregressionat100mg/kginH146xenograftmodel.IHCanalysiswithanti-CD31antibodyshowsthatlenvatinibat100mg/kgdecreasesmicrovesseldensitymorethananti-VEGFantibodyandSTI571treatment[4].PROTOCOLCellAssay[1]H146(1.2×103cells/50μL/well)inSFMcontaining0.5%BSAareculturedin96-wellmulti-plates.Afterovernightcultureat37°C,SFM(150μL/well)containing0.5%FBSandseveralconcentrationsofSCFareaddedwithorwithoutseveralconcentrationsofcompound.Afterculturefor72hr,theratiosofsurvivingcellsaremeasuredbyWST-1.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalFemaleBALB/cnudemice(8-12weeksold,20-25g)aremaintainedunderclean-roomconditions.H146Administration[1]tumorcells(6.5×106)areimplantedsubcutaneously(s.c.)intotheflankregionofmice.Twelvedaysafterinoculation,micearerandomizedintocontrol(n=12)andtreatment(n=6orn=5)groupsandthispointintime2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEisidentifiedasday1.LenvatinibandSTI571,andVEGFneutralizationantibodyaresuspendedin0.5%methylcelluloseandsaline,respectively,andadministeredorallytwiceadayforlenvatinibandSTI571andtwiceaweekforantibodyfromday1today21.Tumorvolumeismeasuredontheindicateddaysandcalculated.Antitumoractivityisshownasarelativetumorvolume(RTV=calculatedtumorvolumeatindicateddays/volumeonday1).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•EMBOJ.2021Apr28;e106771.•JTranslMed.2022Mar7;20(1):116.•BiomedPharmacother.2022Jan;145:112391.•CellDeathDiscov.2021Nov18;7(1):359.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KudoM,etal.LenvatinibversusBay43-9006infirst-linetreatmentofpatientswithunresectablehepatocellularcarcinoma:arandomisedphase3non-inferioritytrial.Lancet.2018Mar24;391(10126):1163-1173.[2].SuyamaK,etal.Lenvatinib:APromisingMolecularTargetedAgentforMultipleCancers.CancerControl.2018Jan-Dec;25(1):1073274818789361.[3].MatsuiJ,etal.E7080,anovelinhibitorthattargetsmultiplekinases,haspotentantitumoractivitiesagainststemcellfactorproducinghumansmallcelllungcancerH146,basedonangiogenesisinhibition.IntJCancer.2008,122(3),664-671.[4].MatsuiJ,etal.Multi-kinaseinhibitorE7080suppresseslymphnodeandlungmetastasesofhumanmammarybreasttumorMDA-MB-231viainhibitionofvascularendothelialgrowthfactor-receptor(VEGF-R)2andVEGF-R3kinase.Cl