Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENintedanibCat.No.:HY-50904CASNo.:656247-17-5Synonyms:BIBF1120分?式:C??H??N?O?分?量:539.62作?靶點(diǎn):PDGFR;VEGFR;FGFR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:11.5mg/mL(21.31mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8532mL9.2658mL18.5316mL5mM0.3706mL1.8532mL3.7063mL10mM0.1853mL0.9266mL1.8532mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：0.5%HEC1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:10mg/mL(18.53mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.32mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.25mg/mL(2.32mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Nintedanib(BIBF1120)?種有效的三重?管激酶抑制劑，抑制VEGFR1/2/3，F(xiàn)GFR1/2/3和PDGFRα/β的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].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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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