JNJ-38158471-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEJNJ-38158471Cat.No.:HY-18317CASNo.:951151-97-6分?式:C??H??ClN?O?分?量:364.79作?靶點(diǎn):VEGFR;RET;c-Kit作?通路:ProteinTyrosineKinase/RTK儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性JNJ-38158471?種耐受良好，有?服活性的?選擇性VEGFR-2抑制劑，IC50值為40nM。JNJ-38158471還抑制Ret和Kit，IC50值分別為180和500nM。IC50&TargetVEGFR-2RETc-Kit40nM(IC50)180nM(IC50)500nM(IC50)體外研究JNJ-38158471(1-500nM;1hour)inhibitsVEGF-stimulatedVEGFR-2autophosphorylationinHUVECs[1].JNJ-38158471(50-1000nM;12-16hours)signi?cantlyinhibitsVEGF-dependentHUVECmigration.CellulartoxicityisnotobservedfollowingJNJ-38158471treatmentofHUVECs[1].WesternBlotAnalysis[1]CellLine:Humanumbilicalveinendothelialcells(HUVECs)Concentration:1,10,100,500nMIncubationTime:1hourResult:Reducedphospoho-VEGFR2levelsat95,88,77and73%withtheconcentrationof500,100,10and1nM,respectively.體內(nèi)研究JNJ-38158471(10or100mg/kg;p.o.;once-daily)inhibitsVEGF-inducedcornealneovascularization[1].JNJ-38158471(10-200mg/kg;p.o.)inhibitsthegrowthofhumantumorxenograftsinadose-dependentmannerinbothA431andHCT116models.JNJ-38158471treatmentiswelltolerated,followingcontinuous1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEadministrationfor24days,bodyweightswerecomparablewithcontrolanimals[1].JNJ-38158471(100mg/kg;p.o.;once-daily)treatmentshowsstatisticallysigni?cantactivitycomparewithvehicletreatanimals.ThebodyweightsofbothJNJ-38158471-treatedandvehicle-treatedgroupswerecomparableatstudyend[1].AnimalModel:FemaleC57BL/6JmiceareimplantedwithrhVEGF165[1]Dosage:10or100mg/kgAdministration:Dailyoraladministrationfor6daysResult:Causedamarkedandapparentlydose-dependentinhibitionofVEGF-dependentbloodvesselformation(100mg/kg,resultedin83%inhibition;10mg/kg,resultedin15%inhibition).AnimalModel:Femaleathymicnudemice;5-6weeks;implantedsubcutaneouslyhumancolorectalcarcinomacells(HCT116)orhumanepidermoidcarcinomacells(A431)[1]Dosage:10,50,100,200mg/kgAdministration:Oraladministrationfor35daysResult:Achievedoptimumef?cacywiththedosefrom100to200mg/kgdaily.AnimalModel:Femaleathymicnudemice;5-6weeks;implantedsubcutaneouslyhumanskinmelanomacells(A375)[1]Dosage:100mg/kgAdministration:Once-dailyoraladministrationfor28daysResult:Inhibited90%growthoftumorwithdailydosesof100mg/kg.AnimalModel:FemaleC57BL/6J-ApcMinmice;5weeksofage[1]Dosage:100mg/kgAdministration:Once-dailyoraladministrationfortwoweeksResult:InhibitedpolypformationinthetransgenicAPCmin-mousemodel.REFERENCES[1].KennethRL,et,al.AHighlySelective,OrallyBioavailable,VascularEndothelialGrowthFactorreceptor-2TyrosineKinaseInhibitorHasPotentActivityinVitroandinVivo.Angiogenesis.2009;12(3):287-96.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidat