Nintedanib-BIBF-1120-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENintedanibCat.No.:HY-50904CASNo.:656247-17-5Synonyms:BIBF1120分⼦式:C₃₁H₃₃N₅O₄分⼦量:539.62作⽤靶点:PDGFR;VEGFR;FGFR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:11.5mg/mL(21.31mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8532mL9.2658mL18.5316mL5mM0.3706mL1.8532mL3.7063mL10mM0.1853mL0.9266mL1.8532mL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：0.5%HEC1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:10mg/mL(18.53mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.32mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.25mg/mL(2.32mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Nintedanib(BIBF1120)⼀种有效的三重⾎管激酶抑制剂，抑制VEGFR1/2/3，FGFR1/2/3和PDGFRα/β的IC50值分别为34nM/13nM/13nM，69nM/37nM/108nM和59nM/65nM。IC50&TargetVEGFR1VEGFR2VEGFR3FGFR134nM(IC50)13nM(IC50)13nM(IC50)69nM(IC50)FGFR2FGFR3PDGFRαPDGFRβ37nM(IC50)108nM(IC50)59nM(IC50)65nM(IC50)体外研究Nintedanib(BIBF1120)bindstotheATP-bindingsiteinthecleftbetweentheaminoandcarboxyterminallobesofthekinasedomain.Nintedanib(BIBF1120)inhibitsproliferationofPDGF-BBstimulatedBRPswithEC50of79nMincellassays.Nintedanib(BIBF1120)(100nM)blocksactivationofMAPKafterstimulationwith5%serumplusPDGF-BB.Nintedanib(BIBF1120)preventsPDGF-BBstimulatedproliferationwithanEC50of69nMinculturesofhumanvascularsmoothmusclecells(HUASMC)[1].体内研究Nintedanib(BIBF1120)(25-100mg/kgdailyp.o.)ishighlyactiveinalltumormodels,includinghumantumorxenograftsgrowinginnudemiceandasyngeneicrattumormodel.Thisisevidentinthemagneticresonanceimagingoftumorperfusionafter3days,reducingvesseldensityandvesselintegrityafter5days,andprofoundgrowthinhibition[1].Nintedanib(BIBF1120)isorallyavailableanddisplaysencouragingefficacyininvivotumormodelswhilebeingwelltolerated[2].PROTOCOLKinaseAssay[2]EnzymeactivityisassayedinthepresenceorabsenceofserialdilutionsofBIBF1120performedin25%DMSO.Eachmicrotiterplatecontainsinternalcontrolssuchasblank,maximumreaction,andhistoricalreferencecompound.Allincubationsareconductedatroomtemperatureonarotationshaker.10μLofeachBIBF1120dilutionisaddedto10μLofdilutedkinase(0.8μg/mLVEGFR2,10mMTrispH7.5,2mMEDTA,and2mg/mLBSA)andpreincubatedfor1hour.Thereactionisstartedbyadditionof30μLofsubstratemixcontaining62.4mMTrispH7.5,2.7mMDTT,5.3mMMnCl2,13.3mMMg-acetate,0.42mMATP,0.83mg/mLPoly-Glu-Tyr(4:1),and1.7μg/mLPoly-Glu-Tyr(4:1)-biotinandincubatedfor1hour.Thereactionisstoppedbyadditionof50μLof250mMEDTA,20mMHEPES,pH7.4.90μLofthereactionmixistransferredtoastreptavidinplateandincubatedfor1-2hours.AfterthreewasheswithPBStheEU-labeledantibody,PY20isadded(recommendeddilution1:2000of0.5mg/mLlabeledantibodyinDELFIAassaybuffer).ExcessivedetectionantibodyisremovedbythreeishesofDELFIAwashingbuffer.Then10minutes2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEbeforemeasurementonthemultilabelreader,eachwellisincubatedwith100μLofDELFIAenhancementsolution.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalFive-week-oldto6-wk-oldathymicNMRI-nu/nufemalemice(21-31g)areusedfortheassay.AfterAdministration[1]acclimatization,miceareinoculatedwith1to5×106(in100μL)FaDu,Caki-1,SKOV-3,H460,HT-29,orPAC-120otherightflankoftheanimal.Afteracclimatization,F344Fischerratsareinjectedwith5×106(in100μL)GS-9Lotherightflankoftheanimal.Forpharmacokineticanalysis,bloodisisolatedatindicatedtimepointsfromtheretroorbitalplexusofmiceandplasmaisanalyzedusinghighperformanceliquidchromatography-massspectrometrymethodology.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.7Jul2022.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•SciAdv.2022Jun17;8(24):eabn4564.•BrJCancer.2020Mar;122(7):986-994.•CellChemBiol.2022Jun9;S2451-9456(22)00201-X.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HilbergF,etal.BIBF1120:tripleangiokinaseinhibitorwithsustainedreceptorblockadeandgoodantitumorefficacy.CancerRes,2008,68(12),4774-4782.[2].RothGJ,etal.Design,synthesis,andevaluationofindolinonesastripleangiokinaseinhibitorsandthediscoveryofahighlyspecific6-methoxycarbonyl-substitutedindo