Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMA242Cat.No.:HY-112816CASNo.:1049704-18-8分?式:C??H??ClF?N?O?S分?量:579.98作?靶點:MDM-2/p53;Apoptosis作?通路:Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性MA242特異性的MDM2和NFAT1雙重抑制劑。MA242以?親和?直接結合MDM2和NFAT1，誘導MDM2和NFAT1蛋?降解，并抑制NFAT1介導的MDM2轉錄。MA242在胰腺癌細胞系中誘導凋亡[1]。IC50&TargetMDM2,NFAT1[1]體外研究MA242(0.05-5μM;72hours)significantlyinhibitspancreaticcancercellgrowth,withIC50srangingfrom0.1to0.4μM,regardlessofthep53statusofthecells.However,MA242showsminimaleffectsonthegrowthofnormalHPDEcells(IC50=5.81μM),indicatingthatMA242hasselectiveeffectsagainstcancercells[1].MA242(0.1-0.5μM;24hours)significantlydecreasestheMDM2andNFAT1proteinlevelsatalowconcentrationinallthreecelllines[1].MA242decreasescellproliferationandinducesapoptosisinpancreaticcancercelllinesregardlessofp53status[1].MA242aloneorincombinationwithGemcitabineinhibitspancreatictumorgrowthandmetastasiswithoutanyhosttoxicity[1].MA242exertscytotoxicityagainsthepatocellularcarcinoma(HCC)cellsbyinhibitingtheNFAT1-MDM2pathwayinvitro,independentofp53.MA242showsselectivecytotoxicityagainstHCCcells,withIC50valuesrangingfrom0.1-0.31μM[2].CellViabilityAssay[1]CellLine:ThehumanpancreaticcancerHPAC,Panc-1,AsPC-1,Mia-Paca-2andBxPC-3celllines;Thehumanpancreaticductalepithelium(HPDE)cellline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration: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.體內研究MA242(IP;2.5,5,10mg/kg)suppressesorthotopicpancreatictumorgrowthinvivo,independentofp53[1].Therewerenosignificantdifferencesintheaveragebodyweightsbetweenthevehicle-andMA242-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.戶使?本產品發(fā)表的科研?獻?BiochemPharmacol.2020Apr;174:113795.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WangW,etal.DiscoveryandCharacterizationofDualInhibitorsofMDM2andNFAT1forPancreaticCancerTherapy.CancerRes.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2018Oct1;78(19):5656-5667.[2].WeiWang,etal.MDM2-NFAT1dualinhibitor,MA242:Effectiveagainsthepatocellularcarcinoma,independentofp53.CancerLett.2019Sep10;459:156-167.McePdfHeightCaution:Producthas