Evo312-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEvo312Cat.No.:HY-169006CASNo.:2820245-53-0分⼦式:C₂₁H₁₉N₃O₃分⼦量:361.39作⽤靶点:Apoptosis;PKC作⽤通路:Apoptosis;Epigenetics;TGF-beta/Smad储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Evo312蛋⽩激酶CβⅠ(PKCβⅠ)的抑制剂(IC50为117.34nM)且有剂量依赖性。Evo312通过抑制PKCβⅠ蛋⽩表达，引起PANC-GR(获得性耐吉西他滨PC细胞)细胞周期阻滞和凋亡。Evo312在胰腺癌细胞PANC-1和PANC-GR细胞中有抗增殖作⽤，IC50为0.08μM和0.07μM，在⼈正常胰腺导管上⽪细胞HPDE6-c7中IC50为2.95μM。Evo312在PANC-GR细胞移植⼩⿏模型中表现出抗肿瘤活性[1]。IC50&TargetPKC-βIPKC-βI117.34nM(IC50)117.34nM(IC50)体外研究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—您⾝边的抑制剂⼤师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.体内研究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—您⾝边的抑制剂⼤师www.MedChemE[1].EunSeoBae,etal.Evo312:AnEvodiamineAnalogandNovelPKCβIInhibitorwithPotentAntitumorActivityinGemcitabine-ResistantPancreaticCancer.JMedChem.2024Aug16.McePdfHeightCaution:Producthasnotbeenful