Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESkp2-IN-4Cat.No.:HY-174346分子式:C??H??N?分子量:377.44作用靶點(diǎn):E1/E2/E3Enzyme作用通路:MetabolicEnzyme/Protease儲(chǔ)存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 Skp2-IN-4是一種Skp2抑制劑，對(duì)Skp2-Cks1結(jié)合的IC50為0.38μM。Skp2-IN-4增強(qiáng)抗腫瘤活性，通過靶向Skp2，抑制腫瘤增殖并誘導(dǎo)S期細(xì)胞阻滯。Skp2-IN-4通過抑制腫瘤細(xì)胞干性，顯著增強(qiáng)NCl-H1299異種移植小鼠模型中對(duì)Cisplatin(HY-17394)的化療敏感性，具有肺癌和食道癌研究潛力[1]。體外研究Skp2-IN-4(Compound10h)potentlyinhibitstumoractivitywithIC50sof11.24and10.32μMforlungcancerNCl-H1299andesophagealcancerKYSE-510cells,respectively[1].Skp2-IN-4(4h)increasestheprotein'sstabilityofSkp2atthetemperaturerangeof57-68°CanddisturbsthebindingofSkp2andCks1inKYSE-510andNCl-H1299cells[1].Skp2-IN-4(2.5-10μM,1-10days)dosedependentlyinhibitscellcolonyformationandDNAsynthesisinKYSE-510andNCl-H1299cells[1].Skp2-IN-4(5-15μM,48h)dosedependentlyreducestheSkp2expression,inducescellularaccumulationofitssubstrates(p21andp27)andarrestscellcycleatSphasewithgreatefficacyat10μMinKYSE-510andNCl-H1299cells[1].Skp2-IN-4(10μM,48h)significantlyinhibitssphereformationandcellclonogenicity,inducesG2/Mphasecellcyclearrestandapoptosis,aswellassuppressingtheproteinlevelsofCD44,Nanog,OCT4andSOX2(tumorstemnessmarkers)withcombinationofCisplatininNCl-H1299cells[1].Immunofluorescence[1]CellLine:KYSE-510cells,NCl-H1299cellsConcentration:5,10,15μMIncubationTime:48h1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEResult:SignificantlydownregulatedtheexpressionofSkp2inadose-dependentmannerinKYSE-510andNCl-H1299cells.Increasedtheintracellularlevelsofp21andp27(substrates)inadose-dependentmannerinKYSE-510andNCl-H1299cells.WesternBlotAnalysis[1]CellLine:KYSE-510cells,NCl-H1299cellsConcentration:5,10,15μMIncubationTime:48hResult:Dose-dependentlydecreasedtheproteinlevelofSkp2butsignificantlyincreasedthep21andp27expressioninKYSE-510andNCl-H1299cells.CellCycleAnalysis[1]CellLine:KYSE-510cells,NCl-H1299cellsConcentration:5,10,15μMor12.5μg/mLCisplatinIncubationTime:48hResult:Inducedadose-dependentSphasearrestinKYSE-510andNCl-H1299cells.CausedinasubstantialcellcycleblockadewiththeSphasecellpopulationfrom17.51%to41.92%inKYSE-510cellsaswellassimilarresultinNCl-H1299cells.SignificantlyinducedG2/M-phasecellcyclearrestat10μMwithcombinationofCisplatininNCl-H1299cells.CellProliferationAssay[1]CellLine:KYSE-510cells,NCl-H1299cellsConcentration:2,5,10μMIncubationTime:7daysResult:Effectivelyinhibitedcellcolonyformationinaconcentration-dependentlymanner.體內(nèi)研究Skp2-IN-4(Compound10h)(25?mg/kg,p.o.,every2dayfor20days)increasesthechemosensitivityofNCl-H1299cellstoCisplatinandpotentlyinhibitstumorgrowthintheNCl-H1299xenograftmicemodel[1].AnimalModel:NOD-SCIDmice(6weeksold)wereinjectedintotherightaxillawithNCl-H1299cells(1?×?107cells/mouse)[1].Dosage:25?mg/kgorCisplatin(5mg/kg)2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEAdministration: Oralgavage(p.o.),Cisplatin(i.p.),every2dayfor20daysandthencollectedtumorsandmajororgantissues.Result: Significantlyinhibitedtumorgrowth,andreducedtumorvolumeandweightwithcombinationofCisplatininNCl-H1299xenograftmicemodel.InducednoobvioustoxicitywithcombinationofCisplatininNCl-H1299xenograftmicemodel.REFERENCESHuK,etal.Molecularhybridizationstrategy-discoveryof2,3-diarylpyrazinederivativesaspotentSkp2inhibitorswithimprovedanti-tumoractivityandenhancedcisplatinsensitivity.EurJMedChem.2025Oct5;295:117788.McePdfHeightCauti