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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENintedanibesylateCat.No.:HY-11106CASNo.:656247-18-6Synonyms:BIBF1120esylate分⼦式:C₃₃H₃₉N₅O₇S分⼦量:649.76作⽤靶点:PDGFR;VEGFR;FGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:66.67mg/mL(102.61mM;Needultrasonic)H2O:16.67mg/mL(25.66mM;Needultrasonic)Ethanol:3.08mg/mL(4.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.5390mL7.6951mL15.3903mL5mM0.3078mL1.5390mL3.0781mL10mM0.1539mL0.7695mL1.5390mL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(sealedstorage,awayfrommoisture)。-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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.85mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.85mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.85mM);Clearsolution4.请依序添加每种溶剂：20%HP-β-CDinsalineSolubility:20mg/mL(30.78mM);Clearsolution;Needultrasonic5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.85mM);Clearsolution6.请依序添加每种溶剂：50%PEG300>>50%salineSolubility:10mg/mL(15.39mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Nintedanibesylate(BIBF1120esylate)⼀种有效的VEGFR1/2/3，FGFR1/2/3和PDGFRα/β三重抑制剂，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].PROTOCOLAnimalFive-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,bloodis2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEisolatedatindicatedtimepointsfromtheretroorbitalplexusofmiceandplasmaisanalyzedusinghighperformanceliquidchromatography-massspectrometrymethodology[1].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-substitutedindolinone(BIBF1120).JMedChem,2009,52(14),4466-4480.[3].SuzukiN,etal.Effectofanoveloralchemotherapeuticagentcontainingacombinationoftrifluridine,tipiracilandthenoveltripleangiokinaseinhibitornintedanib,onhumancolorectalcancerxenografts.OncolRep.