Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemESkp2inhibitor1Cat.No.:HY-149293CASNo.:2760612-63-1分子式:C??H??ClN?O分子量:406.91作用靶點(diǎn):E1/E2/E3Enzyme作用通路:MetabolicEnzyme/Protease儲存方式: 4°C,sealedstorage,awayfrommoistureandlightInsolvent:-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(122.88mM;Needultrasonic)SolventMass1mg5mg10mgConcentration制備儲備液1mM2.4575mL12.2877mL24.5755mL5mM0.4915mL2.4575mL4.9151mL10mM0.2458mL1.2288mL2.4575mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存方式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C儲存時，請在6個月內(nèi)使用，-20°C儲存時，請在1個月內(nèi)使用。BIOLOGICALACTIVITY生物活性Skp2inhibitor1(compound14i)是一種Skp2抑制劑，干擾Skp2-Cks1相互作用，IC50為2.8μM。Skp2inhibitor1也具有抗癌活性[1]。IC50&TargetGrowtharrest-specificprotein6(Gas6)-CellCyclinKinaseSubunit1(Cks1)[1]IC50：2.8μM(Growtharrest-specificprotein6,Gas6;CellCyclinKinaseSubunit1,Cks1)[1]1/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemE體外研究Skp2inhibitor1(2.8μM,72h)interferestheSkp2?Cks1interaction,againstPC-3andMGC-803cellswithIC50valuesof4.8and7.0μM,respectively[1].Skp2inhibitor1(10μM,48h)inhibitstheproliferationandmigrationofPC-3andMGC-803cell,causingthemtoblockintheSphaseandpromotecellapoptosis[1].CellViabilityAssay[1]CellLine:PC-3,MGC-803Concentration:0-10μMIncubationTime:72hResult:AgainsttheSkp2?Cks1interactionwithanIC50valueof2.8μM,andagainstPC-3andMGC-803cellswithIC50valuesof4.8and7.0μM,respectively.ApoptosisAnalysis[1]CellLine:PC-3,MGC-803Concentration:2.5μM,5μM,10μMIncubationTime:0-48hResult:LeadedtocellcycleS-phasearrestinadose-dependentmanner,andinducedapoptosisinadose-dependentmanner,suchasnuclearfragmentation,condensation,andcellshrinkage.CellProliferationAssay[1]CellLine:PC-3,MGC-803Concentration:0.5μM,1μM,2μMIncubationTime:10daysResult:Inhibitedcolony-formingabilitiesinadose-dependentmanner.CellMigrationAssay[1]CellLine:PC-3,MGC-803Concentration:2.5μM,5μM,10μMIncubationTime:48hResult:Inhibitedmigrationinadose-dependentmanner.CellInvasionAssay[1]2/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemECellLine:PC-3,MGC-803Concentration:0.5μM,1μM,2μMIncubationTime:48hResult:Inhibitedinvasioninadose-dependentmanner.WesternBlotAnalysis[1]CellLine:PC-3,MGC-803Concentration:2.5μM,5μM,10μMIncubationTime:0-48hResult:InhibitedtheproteinlevelsofSkp2inadose-dependentmanner,restoredtheexpressionofp21andp27inatime-dependentmanner.體內(nèi)研究Skp2inhibitor1(50mg/kg,intraperitonealinjection/2day,21days)inhibitstumorgrowthsignificantlyinNOD-SCIDxenograftmodelswithoutobvioustoxicity.Inaddition,thetumortreatedwithSkp2inhibitor1(50mg/Kg/2day)wascompletelysuppressedinvivo[1].Skp2inhibitor1decreasestumormalignancyviasuppressingtheSkp2signalpathwayandincreasetheproportionofapoptosisinthetumortissue[1].PharmacokineticParametersofCompound14iinthePlasmaandTumorTissue[1]藥代動力學(xué)分析[1]PKparametersplasmatumortissuet1/214.1±1.5(h)12.6±7.8(h)Cmax176.1±30.3(ng/mL)182.0±80.9(ng/g)AUClast3231.5±407.2(h.ng/mL)2443.9±474.9(h.ng/g)AUCINF3551.5±465.3(h.ng/mL)2636.0±619.7(h.ng/g)VZ143.3±9.2(L/kg)170.8±80.1(mg/kg)CL7.1±0.8(L/h/kg)15.7±4.2(mg/h/kg)MRTlast13.4±0.64(h)9.9±2.5(h)t1/2of14iintheLiverMicrosomesandLiverS9ofDifferentSpecies[1]體外代謝分析[1]specieshumanratmouset1/2livermicrosomes66.016.315.3t1/2liverS964.815.416.5AnimalModel:ThexenograftmodelsofPC-3andMGC-803cellsinNOD-SCIDmice[1].Dosage:10mg/kg;25mg/kg,50mg/kgAdministration:Intraperitonealinjection(i.p.)Result:Inhibitedtumorgrowthwithoutobvioustoxicity,thetumorgrowthinhibitionratiowas55.68,71.86,and90.42%with10,25,and50mg/Kg/2day,respectively.REFERENCES3/4 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEZhangK,etal.DiscoveryofNovel1,3-DiphenylpyrazineDerivativesasPotentS-PhaseKinase-AssociatedProtein2(Skp2)InhibitorsfortheTreatmentofCancer.JMedChem.2023Jun8;66(11):7221-7