MA242-free-base-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMA242freebaseCat.No.:HY-112816ACASNo.:1049704-17-7分⼦式:C₂₄H₂₀ClN₃O₃S分⼦量:465.95作⽤靶点:MDM-2/p53;Apoptosis作⽤通路:Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性MA242freebase特异性的MDM2和NFAT1双重抑制剂。MA242freebase以⾼亲和⼒直接结合MDM2和NFAT1，诱导MDM2和NFAT1蛋⽩降解，并抑制NFAT1介导的MDM2转录。MA242freebase在胰腺癌细胞系中诱导凋亡[1]。IC50&TargetMDM2,NFAT1[1]体外研究MA242(0.05-5μM;72hours)freebasesignificantlyinhibitspancreaticcancercellgrowth,withIC50srangingfrom0.1to0.4μM,regardlessofthep53statusofthecells.However,MA242freebaseshowsminimaleffectsonthegrowthofnormalHPDEcells(IC50=5.81μM),indicatingthatMA242hasselectiveeffectsagainstcancercells[1].MA242(0.1-0.5μM;24hours)freebasesignificantlydecreasestheMDM2andNFAT1proteinlevelsatalowconcentrationinallthreecelllines[1].MA242freebasedecreasescellproliferationandinducesapoptosisinpancreaticcancercelllinesregardlessofp53status[1].MA242freebasealoneorincombinationwithGemcitabineinhibitspancreatictumorgrowthandmetastasiswithoutanyhosttoxicity[1].MA242freebaseexertscytotoxicityagainsthepatocellularcarcinoma(HCC)cellsbyinhibitingtheNFAT1-MDM2pathwayinvitro,independentofp53.MA242showedselectivecytotoxicityagainstHCCcells,withIC50valuesrangingfrom0.1-0.31μM[2].CellViabilityAssay[1]CellLine:ThehumanpancreaticcancerHPAC,Panc-1,AsPC-1,Mia-Paca-2andBxPC-3cell1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemElines;Thehumanpancreaticductalepithelium(HPDE)celllineConcentration:0.05,0.5,and5μMIncubationTime:72hoursResult:TheIC50sare0.14,0.14,0.15,0.25,0.40,and5.81μMforPanc-1,Mia-Paca-2,AsPC-1,BxPC-3,HPAC,andHPDEcells,respectively.WesternBlotAnalysis[1]CellLine:ThehumanpancreaticcancerHPAC,Panc-1,andAsPC-1celllinesConcentration:0,0.1,0.2,and0.5μMIncubationTime:24hoursResult:DecreasedtheexpressionofMDM2andNFAT1.体内研究MA242(IP;2.5,5,10mg/kg)freebasesuppressesorthotopicpancreatictumorgrowthinvivo,independentofp53[1].Therewerenosignificantdifferencesintheaveragebodyweightsbetweenthevehicle-andMA242freebase-treatedmiceineitherofthemodels,didnothavesignificanthosttoxicityattheseeffectivedoses[1].AnimalModel:Female4-6-week-oldathymicnudemice(nu/nu,4-6weeks)bearingAsPC-1-LucorPanc-1-Luctumor[1]Dosage:2.5or5mg/kgforPanc-1tumor-bearingmice;10mg/kgforAsPC-1tumor-bearingmiceAdministration:IP;2.5or5mg/kg/d,5d/wkforfiveweeksforPanc-1tumor-bearingmice;IP;10mg/kg/d,5d/wkforthreeweeksforAsPC-1tumor-bearingmiceResult:Resultedin56.1%and82.5%inhibitionoftumorgrowthinnudemicebearingPanc-1orthotopictumors,respectively.SignificantlysuppressedthegrowthofAsPC-1orthotopictumorsby89.5%(P<0.01)comparedwiththetumorsincontrolanimals.LedtoalmostcompletetumorregressioninMD242-treatedmiceinbothmodels.户使⽤本产品发表的科研⽂献•BiochemPharmacol.2020Apr;174:113795.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].WeiWang,etal.DiscoveryandCharacterizationofDualInhibitorsofMDM2andNFAT1forPancreaticCancerTherapy.CancerRes.2018Oct1;78(19):5656-5667.[2].WeiWang,etal.MDM2-NFAT1dualinhibitor,MA242:Effectiveagainsthepatocellularcarcinoma,independentofp53.CancerLett.2019Sep10;459:156-167.McePdfHeightCaution:Produc