Americanin-A-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEAmericaninACat.No.:HY-N18301CASNo.:69506-79-2分子式:C₁₈H₁₆O₆分子量:328.32作用靶点:ATM/ATR;CheckpointKinase(Chk);MDM-2/p53;E1/E2/E3Enzyme;CDK;Mitosis;ReactiveOxygenSpecies(ROS);Apoptosis作用通路:CellCycle/DNADamage;PI3K/Akt/mTOR;Apoptosis;MetabolicEnzyme/Protease;Immunology/Inflammation;NF-κB储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 AmericaninA，一种neolignan，可从Phytolaccaamericana的种子中分离得到。AmericaninA可激活ATM和ATR，从而启动后续的信号转导级联反应，包括Chk1、Chk2以及肿瘤抑制蛋白p53。AmericaninA选择性地靶向Skp2进行降解，从而稳定p27。AmericaninA抑制CyclinB1及其结合伙伴cdc2的活性，以阻止进入有丝分裂(Mitosis)。AmericaninA通过产生过量的ROS诱导细胞凋亡(Apoptosis)。AmericaninA对结直肠癌具有抗肿瘤活性[1]。IC50&TargetChk1Chk2ATMATR体外研究AmericaninA(24–72h)selectivelyinhibitsproliferationofhumancancercells(IC509.0–66.4μM)withnosignificanteffectonMRC-5normalcells,andinhibitsHCT116cellsinaconcentration-andtime-dependentmanner[1].AmericaninA(7.5-30μM;24h)inducesG2/Mcell-cyclearrestinHCT116cells,with30μMincreasingG2/Mphasecellsto38.9%[1].AmericaninA(7.5–30μM;24h)inducesDNAdamageinHCT116cells,asindicatedbyincreasedphosphorylatedH2A.XanddecreasedacetylatedH3[1].AmericaninA(7.5–30μM;48h)inducesapoptosisinHCT116cellsafter48htreatment,with30μMincreasingsub-G1cellsto52.0%[1].CellProliferationAssay[1]CellLine:A549,Caki-1,K562,HCT116,SW480,HCT-15,RKO,MRC-51/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEConcentration:IC₅₀values(9.0–66.4μMforcancercells;>100μMforMRC-5)IncubationTime:24h,48h,72hResult:InhibitedproliferationofA549(IC₅₀39.1μM),Caki-1(IC₅₀66.4μM),K562(IC₅₀12.9μM),HCT116(IC₅₀9.0μM),SW480(IC₅₀27.4μM),HCT-15(IC₅₀12.5μM),RKO(IC₅₀24.4μM)cells;measuredHCT116IC₅₀valuesof24.1μM(24h),9.6μM(48h),8.7μM(72h);showednosignificantinhibitionofMRC-5cells(IC₅₀>100μM).CellCycleAnalysis[1]CellLine:HCT116Concentration:7.5,15,30μMIncubationTime:24hResult:IncreasedtheproportionofG₂/Mphasecellsfrom20.6%(untreated)to38.9%at30μM;increasedsub-G₁cellproportion(apoptosisindicator)concentration-dependently,buttheincreasewasnotsignificantat24h.WesternBlotAnalysis[1]CellLine:HCT116Concentration:7.5,15,30μMIncubationTime:24hResult:SuppressedexpressionofcyclinA,cyclinB1,phosphorylatedcyclinB1(Ser147),CDK2,andcdc2inaconcentration-dependentmanner.\nIncreasedphosphorylationofhistoneH2A.X(Ser139)anddecreasedacetylationofhistoneH3(Lys9)concentration-dependently.ApoptosisAnalysis[1]CellLine:HCT116Concentration:7.5,15,30μMIncubationTime:48hResult:Increasedsub-G₁cellproportionfrom6.5%(untreated)to52.0%at30μM;showedincreasedearlyandlateapoptoticcellsconcentration-dependentlyviaannexinV/FITCstaining.体内研究AmericaninA(5-10mg/kg;i.p.;threetimesaweek)inhibitsHCT116tumorxenograftgrowthinnudemice2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEwith45.0%and55.7%tumorvolumereductionat5and10mg/kg,respectively,viaSkp2-dependentp27stabilization[1].AnimalModel:BALB/c-nu(female,4-6weeksold,HCT116tumorxenograft)[1]Dosage:5mg/kg;10mg/kgAdministration:i.p.;threetimesaweekResult:Reducedtumorvolumesby45.0%(5mg/kg)and55.7%(10mg/kg)comparedtovehicle;Increasedexpressionsofp21andp27,anddecreasedSkp2expressioninexcisedtumors;Showedpronouncedp27staininganddiminishedSkp2andKi-67stainingviaimmunohistochemistry;Observednooverttoxicityorbodyweightchanges.REFERENCESJungC,etal.AntitumorActivityofAmericaninAIsolatedfromtheSeedsofPhytolaccaamericanabyRegulatingtheATM/ATRSignalingPathwayandtheSkp2-p27AxisinHumanColonCancerCells.JNatProd.2015;78(12):2983-2993.McePdfHeightC