MMRi62-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMMRi62Cat.No.:HY-148409CASNo.:352693-80-2分⼦式:C₂₁H₁₅Cl₂N₃O分⼦量:396.27作⽤靶点:Ferroptosis;Apoptosis;Autophagy;MDM-2/p53作⽤通路:Apoptosis;Autophagy储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:62.5mg/mL(157.72mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5235mL12.6177mL25.2353mL5mM0.5047mL2.5235mL5.0471mL10mM0.2524mL1.2618mL2.5235mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(protectfromlight)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。BIOLOGICALACTIVITY⽣物活性MMRi62⼀种铁死亡(ferroptosis)诱导剂，靶向MDM2-MDM4(抑癌因p53负调控因⼦)。MMRi62对胰腺导管腺癌(PDAC)细胞显⽰出p53独⽴的促凋亡(apoptosis)活性，并诱导其⾃噬(autophagy)。MMRi62诱导铁死亡，伴随活性氧增加和铁蛋⽩重链(FTH1)溶酶体降解。MMRi62还可导致突变型p53的蛋⽩酶体降解，并对具有KRAS和TP53⾼频突变特征的原位异种移植PDAC⼩⿏模型具有体内药效。体外研究MMRi62inhibitsproliferation,clonogenic,andspheroidgrowthofpancreaticductaladenocarcinomacell1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE(PDAC)byinductionofcelldeath[1].1MMRi62(3nM-100μM;4h)bindstoRING–RINGheterodimersofMDM2andMDM4withtheKdvalueof1.39μM[2].MMRi62(10nM-1μM;72h)inducesapoptosisandinhibitsleukemiccellswithIC50sof0.34µM(HL60)and0.22µM(HL60VR)[2].MMRi62(5μMand10μM;24h)decreasesMDM2Bautoubiquitination,increasesMDM4ubiquitinationinadose-dependentmanner[2].MMRi62isanE3ligasemodifiercapableofswitchingsubstratepreferencefromMDM2toMDM4[2].MMRi62(5μM;24and72h)inducesapoptosisinap53-independentmanner[2].WesternBlotAnalysis[2]CellLine:WT-p53bearingMV4-11cells;293cellstransfectedwithMDM2BandMDM4Concentration:2,2.5,5,10,40,80,160μMIncubationTime:24hoursResult:IncreasedcleavedPARPproteinandactivatedcaspase3levelinwt-p53bearingMV4-11cellsat2μMfor24h.DecreasedMDM2Bautoubiquitination,increasedMDM4ubiquitinationat5μMand10μMfor24h.InducedMDM2-dependentdegradationofMDM4proteinat5μMinNALM6cells.CellProliferationAssay[2]CellLine:PrimaryAMLpatientcells,NALM6cellsandNALM6shp53cellsConcentration:1,10,25,and50µMIncubationTime:24hoursand72hoursResult:InducedNALM6cellsapoptosisat24handinducedPrimaryAMLpatientcellsat72h.体内研究MMRi62showsanti-tumoractivityinorthotopicxenograftPDACmousemodels,byinhibitingtumorgrowthinmiceassociatedwithdownregulationofNCOA4andmutantp53[1].MMRi62alsocompletelyabrogatesmetastasisoforthotopictumors[1].REFERENCES[1].LiJ,etal.Small-MoleculeMMRi62InducesFerroptosisandInhibitsMetastasisinPancreaticCancerviaDegradationofFerritinHeavyChainandMutantp53.MolCancerTher.2022Apr1;21(4):535-545.[2].LamaR,etal.SmallmoleculeMMRi62targetsMDM4fordegradationandinducesleukemiccellapoptosisregardlessofp53status.FrontOncol.2022Aug5;12:933446.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeenfullyvalidat