Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENintedanibesylateCat.No.:HY-11106CASNo.:656247-18-6Synonyms:BIBF1120esylate分?式:C??H??N?O?S分?量:649.76作?靶點:PDGFR;VEGFR;FGFR作?通路:ProteinTyrosineKinase/RTK儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:66.67mg/mL(102.61mM;Needultrasonic)H2O:16.67mg/mL(25.66mM;Needultrasonic)Ethanol:3.08mg/mL(4.74mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.5390mL7.6951mL15.3903mL5mM0.3078mL1.5390mL3.0781mL10mM0.1539mL0.7695mL1.5390mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.85mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.85mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.85mM);Clearsolution4.請依序添加每種溶劑：20%HP-β-CDinsalineSolubility:20mg/mL(30.78mM);Clearsolution;Needultrasonic5.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(3.85mM);Clearsolution6.請依序添加每種溶劑：50%PEG300>>50%salineSolubility:10mg/mL(15.39mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Nintedanibesylate(BIBF1120esylate)?種有效的VEGFR1/2/3，F(xiàn)GFR1/2/3和PDGFRα/β三重抑制劑，IC50值分別為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)體外研究Nintedanib(BIBF1120)bindstotheATP-bindingsiteinthecleftbetweentheaminoandcarboxyterminallobesofthekinasedomain.Nintedanib(BIBF1120)inhibitsproliferationofPDGF-BBstimulatedBRPswithEC50of79nMincellassays.Nintedanib(BIBF1120)(100nM)blocksactivationofMAPKafterstimulationwith5%serumplusPDGF-BB.Nintedanib(BIBF1120)preventsPDGF-BBstimulatedproliferationwithanEC50of69nMinculturesofhumanvascularsmoothmusclecells(HUASMC)[1].體內(nèi)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?邊的抑制劑?師www.MedChemEisolatedatindicatedtimepointsfromtheretroorbitalplexusofmiceandplasmaisanalyzedusinghighperformanceliquidchromatography-massspectrometrymethodology[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?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.