Tubulin-VEGFR-2-IN-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETubulin/VEGFR-2-IN-2Cat.No.:HY-180292CASNo.:2882998-56-1分⼦式:C₂₀H₂₂N₄O₃分⼦量:366.41作⽤靶点:VEGFR;Microtubule/Tubulin;ReactiveOxygenSpecies(ROS);Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;CellCycle/DNADamage;

Cytoskeleton;Immunology/Inflammation;Metabolic

Enzyme/Protease;NF-κB;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Tubulin/VEGFR-2-IN-2⼀种具有⼝服活性的tubulin和VEGFR-2双重抑制剂其IC50值分别为3.27μM和0.09μM。Tubulin/VEGFR-2-IN-2通过多途径发挥抗肿瘤作⽤，包括增强活性氧(ROS)⽣成、破坏线粒体膜电位、诱导细胞凋亡(apoptosis)以及阻滞细胞周期。Tubulin/VEGFR-2-IN-2还在体外表现出显著的抗⾎管⽣成特性，能有效抑制内⽪细胞的迁移、侵袭和管腔形成。Tubulin/VEGFR-2-IN-2在体内可抑制⾎管⽣成、肿瘤⽣长及转移。Tubulin/VEGFR-2-IN-2可⽤于⾮⼩细胞癌，乳腺癌，胃癌和淋巴瘤的研究[1]。IC50&TargetVEGFR2Tubulin0.09μM(IC50)3.27nM(IC50)体外研究Tubulin/VEGFR-2-IN-2(compound19d)(48h)displayssuperioranti-proliferativeeffectsacrossapanelofcancercelllines(IC50=0.26,0.19,0.04,0.04,12.06and4.70μMforA549,MCF-7,MGC-803,U937cell,HEK293TandRAW264.7cellsrespectively)[1].Tubulin/VEGFR-2-IN-2(0-20nM,24h)exhibitspotentanti-proliferationeffectsinMGC-803cells[1].Tubulin/VEGFR-2-IN-2(25-100nM,48h)suppressescellproliferationbyinterferingwiththepolymerizationprocessoftubulininMGC-803cells[1].Tubulin/VEGFR-2-IN-2(25-100nM,48h)reducestheMitochondrialmembranepotential,exhibitsapoptosisbyactivatingthecaspasefamilyproteins,inducesconsiderableDNAdamageandoxidativestress,causesG2/Mphasecellcyclearrestandimpairsthemigratoryandinvasiveabilitywithadose-dependentmannerinMGC-803cells[1].Tubulin/VEGFR-2-IN-2(20-80nM,6-8hor48h)inhibitsangiogenesis(includingimpairsangiogenicstructures,destroysthetubularnetwork,decreasesnodes,masterjunctions,segmentlength,totalbranching1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemElength,meshes,andmeandensity)bysuppressingoftheVEGFR-2-drivenPI3K/AKT/MAPKpathwayinhumanumbilicalveinendothelialcell(HUVEC)[1].Tubulin/VEGFR-2-IN-2(20-80nM,48h)inhibitsendothelialcellmigrationandinvasioninHUVEC[1].CellCycleAnalysis[1]CellLine:MGC-803cellsConcentration:25,50,100nMIncubationTime:48hResult:Ledtoaconcentration-dependentincreaseintheproportionofcellsintheG2/Mphase.Immunofluorescence[1]CellLine:MGC-803cellsConcentration:25,50,100nMIncubationTime:48hResult:Transformedfromthetypicalelongated,spindle-likeconfigurationintoaroundedform.ApoptosisAnalysis[1]CellLine:MGC-803cellsConcentration:25,50,100nMIncubationTime:48hResult:Exhibitedconcentration-dependentapoptosis.WesternBlotAnalysis[1]CellLine:MGC-803cellsConcentration:25,50,100nMIncubationTime:48hResult:LedAnupregulationofCyt-Candthepro-apoptoticproteinBax,accompaniedbyadownregulationoftheanti-apoptoticproteinBcl-2.IncreasedinγH2AXexpression.LedareductionofCyclinB1andphosphorylatedCdc2(p-Cdc2)expressionandamarkeddownregulationofthecellcycleinhibitorP21.ReducedthephosphorylationofERK,downregulatedthemesenchymalmarkersVimentinandN-cadherin,andupregulatedtheepithelialmarkerE-cadherininadose-dependentmanner.2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemELedtoasignificantreductionintheexpressionofbothFAKandMMP-9.CellProliferationAssay[1]CellLine:MGC-803cellsConcentration:0,1.25,2.5,5,10and20nMIncubationTime:24hResult:Decreasedsignificantlythenumberandthesizeofcoloniesformed.CellMigrationAssay[1]CellLine:MGC-803cellsConcentration:25,50,100nMIncubationTime:48hResult:Exhibitedasignificantreduction.HadaninversecorrelationwiththeinvasivecapacityofMGC-803cells.WesternBlotAnalysis[1]CellLine:HUVECcellsConcentration:20,40and80nMIncubationTime:48hResult:MarkedlyreducedVEGFR-2expressionandattenuatedthephosphorylationofPI3K,AKT,andERK.体内研究Tubulin/VEGFR-2-IN-2(compound19d)(100-400nMin1mLwater,18h)caninhibitsangiogenesisinTg(flk:EGFP)zebrafishembryos[1].Tubulin/VEGFR-2-IN-2(100-400nMin1mLwater,72h)effectivelyinhibitsbothtumorgrowthandmetastasisinvivoinadose-dependentmannerinfluorescentlylabeledMGC-803cellsinduced-Tg(flk:EGFP)zebrafishlarvae[1].AnimalModel:Tg(flk:EGFP)zebrafishembryos[1]Dosage:100nM,200nM,and400nMAdministration:Maintainedin1mLaquaculturewaterwithdifferentdosagefor18hResult:Producedadose-responsivedeclineinboth,intersegmentalvessels(ISVs)countand3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEvessellength.AnimalModel:FluorescentlylabeledMGC-803cells(300-500cells)induced-Tg(flk:EGFP)zebrafishlarvae[1]Dosage:100nM,200nM,and400nMAdministration:Maintainedin1mLaquaculturewaterwithdifferentdosagefor18hResult:Suppressedtumorcellmigrationinadose-dependentmanner.Thetumormasswassignificantlydecreasedatthehighestconcentration.REFERENCES[1].ChuY,etal.Discoveryofnovelaniline-pyrimidineanaloguesasorallybioavailabledualVEGFR-2/tubulininhibitorswithpotentantitumorandanti-