IKKβ-IN-5-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIKKβ-IN-5Cat.No.:HY-180119分⼦式:C₂₃H₂₄FN₇分⼦量:417.48作⽤靶点:IKK;NF-κB;Autophagy作⽤通路:NF-κB;Autophagy储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性IKKβ-IN-5⼀种具有⼝服活性和选择性的IKKβ抑制剂，其IC50值为7.5nM。IKKβ-IN-5可直接抑制IKKβ磷酸化从⽽减弱NFκB介导的炎症与⽣存信号，同时促进⾃噬(autophagy)流。IKKβ-IN-5对IKKβ相较于同激酶IKKα展现出6倍的选择性。IKKβ-IN-5通过双重机制即诱导G₂/M期细胞周期阻滞和激活⾃噬(autophagy)发挥强效的抗增殖作⽤即使在体外炎症刺激条件下亦然。IKKβ-IN-5在体内表现出良好的药代动⼒学特性并抑制肿瘤⽣长。IKKβ-IN-5可⽤于结直肠癌及其他潜在炎症驱动型恶性肿瘤的相关研究[1]。IC50&TargetIKK-β7.5nM(IC50)体外研究IKKβ-IN-5(compoundLP46)(0-2μM,48h)exhibitsrobustantiproliferativeactivityinRKOandHCT116cellsandlowtoxicityinNCM460cells[1].IKKβ-IN-5(0.75-3.0μM,48h)impactsproteinexpressionofIKKβphosphorylationanditsdownstreamtargetIκBαbydirectlyinhibitingthephosphorylationofIKKβinRKOandHCT116cells[1].IKKβ-IN-5(0.75-3.0μM,7days)haslong-termantiproliferativeeffectsinRKOandHCT116cells[1].IKKβ-IN-5(0.75-3.0μM,48h)exertstheantiproliferativeeffectsthroughadualmechanism(includinginducingG2/Mphasecellcyclearrestandactivatingautophagy)eveninthepresenceofinflammatorystimuli,andhasabilitytoblockNF-κBpathwayactivationsuppressingdownstreaminflammatoryresponsesinRKOandHCT116cells[1].IKKβ-IN-5(3μM,48h)directlycounteractsIKKβ-mediatedpro-inflammatoryandantautophagyeffectsinIKKβknockdownCRCcellsorIKKβoverexpressionCRCcells[1].CellViabilityAssay[1]CellLine:HCT116,RKO,andNCM460cells1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:0,0.40.8,1.2,1.6and2.0μMIncubationTime:48hResult:Exhibitedpotentinhibitoryactivity,withIC50valuesof3.94μMforRKOand2.59μMforHCT116.ShowedsignificantlylowertoxicityinNCM460cells,withanIC50of21.25μM.WesternBlotAnalysis[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μMIncubationTime:48hResult:SignificantlyreducedphosphorylationofbothIKKβandIκBαinadose-dependentmanner.InducedgreaterinhibitionofIKKβphosphorylation.HadnosignificantimpactoneithertheexpressionorphosphorylationofTAK1orMAP3K1.CellProliferationAssay[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μMIncubationTime:7daysResult:ObservedDose-dependentsuppressionofcolonyformation.Demonstratedsuperiorefficacyatthehighestdose.CellCycleAnalysis[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μMIncubationTime:48hResult:RevealedasignificantaccumulationofRKOandHCT116cellsintheG2/Mphase.CellProliferationAssay[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μM2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:48hResult:SignificantlyinhibitedDNAsynthesisinbothRKOandHCT116cells.WesternBlotAnalysis[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μMIncubationTime:48hResult:Dose-dependentlyincreasedexpressionlevelsofkeyautophagy-relatedmarkers,Beclin1andLC3A/BbothmarkersinRKOandHCT116cells.EnhancedexpressionofBeclin1andLC3A/BinthesecellsinRKOandHCT116cellswithTNF-α(HY-P1875).Reducedp65expressionandinhibiteditsnucleartranslocationinadose-dependentmanner.RT-PCR[1]CellLine:RKOandHCT116cellsConcentration:0.75,1.5,and3μMIncubationTime:48hResult:SignificantlydownregulatedtheexpressionofTNF-α,IL-6,andIL-1βinadosedependentmanner.WesternBlotAnalysis[1]CellLine:IKKβknockdownCRCcellsorIKKβoverexpressionCRCcellsConcentration:3μMIncubationTime:48hResult:ReducedthephosphorylationlevelsofbothIκBαandp65,whileconcurrentlyincreasingtheexpressionofkeyautophagymarkers,Beclin1andLC3A/BandexhibitedsuperiorefficacyininhibitingIKKβphosphorylationandsuppressingNF-κBsignalinguponTNF-αstimulationinIKKβknockdowncells.Increasedp-IκBαandp-p65levelsandreducedBeclin1andLC3A/BexpressionuponTNF-αstimulationinoverexpressionofIKKβcells.DecreasedNF-κBphosphorylationandrestorationofautophagy-relatedproteinlevels,evenunderTNF-αstimulationandIKKβ-overexpressingconditions.CellViabilityAssay[1]3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HCT116,RKO,andNCM460cellsConcentration:0,0.40.8,1.2,1.6and2.0μMIncubationTime:48hResult:Exhibitedpotentinhibitoryactivity,withIC50valuesof3.94μMforRKOand2.59μMforHCT116.ShowedsignificantlylowertoxicityinNCM460cells,withanIC50of21.25μM.REFERENCES[1].WangK,etal.DiscoveryandStructuralOptimizationofNovel2-AminopyrimidineDerivativesasPotentandSelectiveIKKβInhibitorsfortheTreatmentofColorectalCancer.JMedCh