Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEvo312Cat.No.:HY-169006CASNo.:2820245-53-0分?式:C??H??N?O?分?量:361.39作?靶點:Apoptosis;PKC作?通路:Apoptosis;Epigenetics;TGF-beta/Smad儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Evo312蛋?激酶CβⅠ(PKCβⅠ)的抑制劑(IC50為117.34nM)且有劑量依賴性。Evo312通過抑制PKCβⅠ蛋?表達，引起PANC-GR(獲得性耐吉西他濱PC細胞)細胞周期阻滯和凋亡。Evo312在胰腺癌細胞PANC-1和PANC-GR細胞中有抗增殖作?，IC50為0.08μM和0.07μM，在?正常胰腺導管上?細胞HPDE6-c7中IC50為2.95μM。Evo312在PANC-GR細胞移植??模型中表現(xiàn)出抗腫瘤活性[1]。IC50&TargetPKC-βIPKC-βI117.34nM(IC50)117.34nM(IC50)體外研究Evo312(0-160nM,24h)inhibitsPKCβ1proteinexpressionanddownstreamtargetproteinphosphorylationinPANC-GRcells[1].Evo312(0-160nM,24h)inducesG2/McellcyclearrestinPANC-GRcells,inhibitingtocellmitosis[1].Evo312(0-160nM,48h)inducesapoptosisinPANC-GRcells[1].CellCycleAnalysis[1]CellLine:PANC-GR(anacquiredgemcitabine-resistantPCcellline,celllinePANC-GRwasestablishedinvitrofromPANC-1cellsbyexposinggemcitabinewithgraduallyincreasingconcentrations(0.1?2μM))Concentration:0,40,80,160nMIncubationTime:24hResult:IncreasedthenumberofG2/Mcellsfrom37.53%to58.51%,leadingtomitosis.1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEApoptosisAnalysis[1]CellLine:PANC-GR,PANC-1Concentration:40,80,160nMIncubationTime:48hResult:Increasedtotalcelldeath(includingearlyapoptosis,lateapoptosisandnecrosis)by15.83%,20.63%and24.95%.WesternBlotAnalysis[1]CellLine:PANC-GR,PANC-1Concentration:0,40,80,160nMIncubationTime:24h;48hResult:InhibitedtheexpressionofPKCβ1proteinat24h,andinhibitedthephosphorylationofglycogensynthasekinase3β(GSK3β),proteinkinaseB(Akt),signaltransducerandactivatoroftranscription5(STAT5),andribosomalproteinS6kinaseβ-1(70S6K)inadose-dependentmanner.DownregulatedtheexpressionlevelsofCDK(CDK2andcdc2)andcyclinD1proteinsat24h,whileupregulatedtheexpressionlevelsofcyclinB1andp27proteins.Increasedtheexpressionlevelsofapoptosismarkerscaspase3,caspase8,andcaspase9proteinsat48h.體內(nèi)研究Evo312(5mg/kg,ip.,threetimesaweek,20days)inhibitstumorgrowthinthePANC-GR(Gemcitabine-resistantcells)mousexenograftmodelbyinhibitingPKCβⅠ,whereasgemcitabinetreatmentresultedinnegligibleinhibitoryeffectsontumorgrowth[1].AnimalModel:PANC-GRcellmousexenograftmodel;PANC-1cellmousexenograftmodel[1]Dosage:40mg/kg;5mg/kg,threetimesaweek,20daysAdministration:Intraperitonealinjection(i.p.)Result:Didnotcausemousedeathorsignificanttoxicityatadoseof40mg/kg.Atadoseof5mg/kg,thetumorvolumewasinhibitedby72%,andthetumorweightwasreducedby44.89%comparedwiththedrug-loadedtreatmentgroup,withnosignificanttoxicityorweightchanges,andtheexpressionofPKCβIintumortissuesimplantedwithPANC-GRcellswaseffectivelyinhibited.REFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].EunSeoBae,etal.Evo312:AnEvodiamineAnalogandNovelPKCβIInhibitorwithPotentAntitumorActivityinGemcitabine-ResistantPancreaticCancer.JMedChem.2024Aug16.McePdfHeightCaution:Producthasnotbeenful