Lenvatinib-E7080-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELenvatinibCat.No.:HY-10981CASNo.:417716-92-8Synonyms:E7080分?式:C??H??ClN?O?分?量:426.85作?靶點(diǎn):VEGFR;FGFR;PDGFR;c-Kit;RET作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥12.78mg/mL(29.94mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3427mL11.7137mL23.4274mL5mM0.4685mL2.3427mL4.6855mL10mM0.2343mL1.1714mL2.3427mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：0.5%Methylcellulose/salinewaterSolubility:6.67mg/mL(15.63mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥0.64mg/mL(1.50mM);ClearsolutionBIOLOGICALACTIVITY?物活性Lenvatinib(E7080)?種具有?服活性的，多靶點(diǎn)酪氨酸激酶抑制劑，抑制?管內(nèi)??長(zhǎng)因?受體(VEGFR1-3)，成纖維細(xì)胞?長(zhǎng)因?受體(FGFR1-4)，??板衍??長(zhǎng)因?受體(PDGFR)，?細(xì)胞因?受體(KIT)，轉(zhuǎn)染期間重排(RET)，顯?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)體外研究Lenvatinib(E7080)hasIC50sof4,5.2,22nMforVEGFR2(KDR),VEGFR3(Flt-4),andVEGFR1(Flt-1),respectively.LenvatinibinhibitsPDGFRα,PDGFRβ,FGFR1,andKITwithIC50sof51,39,46,and100nM,respectively[3].體內(nèi)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?邊的抑制劑?師www.MedChemEisidentifiedasday1.LenvatinibandSTI571,andVEGFneutralizationantibodyaresuspendedin0.5%methylcelluloseandsaline,respectively,andadministeredorallytwiceadayforlenvatinibandSTI571andtwiceaweekforantibodyfromday1today21.Tumorvolumeismeasuredontheindicateddaysandcalculated.Antitumoractivityisshownasarelativetumorvolume(RTV=calculatedtumorvolumeatindicateddays/volumeonday1).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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