VEGFR-2-P-gp-IN-1-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEVEGFR-2/P-gp-IN-1Cat.No.:HY-174324分子式:C₂₄H₂₄F₆N₂O₃分子量:502.45作用靶点:VEGFR;P-glycoprotein;Apoptosis作用通路:ProteinTyrosineKinase/RTK;MembraneTransporter/IonChannel;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性VEGFR-2/P-gp-IN-1是一种LicochalconeA(HY-N0372)衍生物，是一种具口服活性的VEGFR-2(IC50=0.885μM)和P-糖蛋白(P-gp)抑制剂。VEGFR-2/P-gp-IN-1通过同步抑制VEGFR-2激酶活性和P-gp药物外排泵功能，实现抗肿瘤增殖并克服化疗耐药性。VEGFR-2/P-gp-IN-1可抑制VEGFR-2以及下游PI3K/AKT信号通路蛋白的磷酸化，诱导细胞凋亡(Apoptosis)，将细胞阻滞在S期，并抑制侵袭性迁移。VEGFR-2/P-gp-IN-1在HeLa/DDP细胞异种移植瘤模型中展现出强大的体内抗肿瘤作用。VEGFR-2/P-gp-IN-1可用于宫颈癌的研究[1]。体外研究VEGFR-2/P-gp-IN-1(CompoundA20)(1-100μM,48h)significantlyinhibitsproliferationofcervicalcancercells(includingdrug-resistantstrains)[1].VEGFR-2/P-gp-IN-1(1-6μM,24h)overcomescervicalcancerdrugresistancethroughdual-targetinhibitionofVEGFR-2phosphorylationandP-gpeffluxfunction[1].VEGFR-2/P-gp-IN-1(1-4μM,24h)inducesapoptosisthroughactivationofapoptoticpathways,blockscellcycleprogressionatSphase,andsignificantlysuppressesinvasionandmigrationinHeLa/DDPcells[1].WesternBlotAnalysis[1]CellLine:HeLa-DDPcells,HUVECcellsConcentration:1μM,2μM,4μM,6μMIncubationTime:24hResult:Dose-dependentlyinhibitedVEGFR-2anddownstreamPI3K/AKTphosphorylation.Upregulatedthepro-apoptoticproteinBax,downregulatedtheanti-apoptoticproteinBcl-2,anddidnotaltertheexpressionlevelofP-gpprotein.CellViabilityAssay[1]1/4 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemECellLine:HeLa/DDPdrugresistantcells,HeLa/PTXdrugresistantcells,HeLa/ADRdrugresistantcellsConcentration:1.0μM,6.25μM,12.5μM,25μM,50μM,100μMIncubationTime:48hResult:Showedthemostsignificantinhibitoryactivityagainstthesethreedrug-resistantcervicalcancercelllines,withIC50valuesof3.69μM(HeLa/DDP),4.81μM(HeLa/PTX),and5.98μM(HeLa/ADR),comparedwithHeLacells,theresistanceindices(RIs)were1.16,1.51,and1.87,respectively.ApoptosisAnalysis[1]CellLine:HeLa/DDPcellsConcentration:1μM,2μM,4μMIncubationTime:24hResult:InducedapoptosisinHeLacellsatarateof92.3%ataconcentrationof4μM.InducedapoptosisinHeLa/DDPcellsatarateof94.5%ataconcentrationof4μM.CellCycleAnalysis[1]CellLine:HeLa/DDPcellsConcentration:1μM,2μM,4μMIncubationTime:24hResult:InducedS-phasearrestinHeLacellsat39.32%ataconcentrationof4μM.InducedS-phasearrestinHeLa/DDPcellsat39.04%ataconcentrationof4μM.Immunofluorescence[1]CellLine:HeLa/DDPcellsConcentration:1μM,2μM,4μMIncubationTime:24hResult:Reducedthefluorescenceintensityofp-VEGFR-2inHeLa/HeLa-DDPcellsinadose-dependentmanner.CellInvasionAssay[1]CellLine:HeLa/DDPcells2/4 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEConcentration:1μM,2μM,4μMIncubationTime:24hResult:ReducedinvasivepotentialofHeLa/DDPcellsto209,142,and54cellsatconcentrationsof1,2,and4μM.ReducedinvasivepotentialofHeLacellsto360,219,and106cellsatconcentrationsof1,2,and4μM.CellMigrationAssay[1]CellLine:HeLa/DDPcellsConcentration:1μM,2μM,4μMIncubationTime:24hResult:ReducedpenetrationcapacityofHeLa/DDPcellsintotheventricularmembraneto268,178,and85cellsatconcentrationsof1,2,and4μM,respectively.ReducedpenetrationcapacityofHeLacellsthroughtheventricularmembraneto583,286,and226cellsatconcentrationsof1,2,and4μM.体内研究VEGFR-2/P-gp-IN-1(CompoundA20)(10-40mg/kg,i.g.,dailyfor14days)demonstratestherapeuticpotentialagainstcisplatin-resistantcervicalcancerinHeLa/DDPcellxenograftmousemodels,withafavorablesafetyprofileandnosignificanttoxicityobserved[1].AnimalModel:HeLa/DDPcellxenograftmodelestablishedinBALB/Cnudefemalemice(4-5weeks)[1]Dosage:10mg/kg,20mg/kg,40mg/kgAdministration:Dailyintragastricgavage(i.g.),atthecorrespondingdosesfor14days.Result:Suppressedgraftedtumorsby70.9%,72.2%,and89.5%atdosesof10,20,and40mg/kg(positivecontrolsorafenib20mg/kg:36.1%reduction).Inhibitedgrowthofdrug-resistantcervicalcancerxenograftsdose-dependentlyviaoraladministration.Maintainedcomparablebodyweightacrossallgroups.AnimalModel:FemaleKunmingmice(5weeks,20-22g)[1]Dosage:200mg/kgAdministration:Dailyintragastricgavage(i.g.),atthecorrespondingdosesfor14days.Result:Causednomortalityorsignificantbodyweightchangesversuscontrolsinacutemouse3/4 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEtoxicitytesting.Inducednormalliver/kidneyfunctionwithoutnecrosis,structuraldisorder,orinflammatoryinfiltrationinacutemousetoxicitytesting.Demonstratedsafetyat200mg/kgwithoutsignificanttoxicity.REFERENCESZhengYang,etal.Design,synthesis,andinvitroandinvivoanti-drugresistantcervicalcanceractivityofnovellicochalconeAderivativesbasedondualtargetingofVEGFR