ATM-IN-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEATM-IN-2Cat.No.:HY-174989分子式:C₂₅H₂₁N₃O₃S分子量:443.52作用靶点:ATM/ATR;Apoptosis作用通路:CellCycle/DNADamage;PI3K/Akt/mTOR;Apoptosis储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性JAK2-IN-13是一种选择性且口服有效的ATM抑制剂，其IC50s为4nM。ATM-IN-2具有高度的激酶选择性(相对于PIKK家族成员的选择性超过700倍)。ATM-IN-2通过抑制ATM磷酸化和下游信号通路(p53、H2AX)发挥抗肿瘤作用并促进细胞凋亡(apoptosis)。ATM-IN-2可用于实体瘤，如结肠癌的研究[1]。IC50&TargetATM4nM(IC50)体外研究ATM-IN-2(Compound25a)(0-10000nM,6-7days)showsgoodinhibitoryactivityagainstHEL116andSW620cells,withIC50valuesof58.2and66.6nM,andeffectivelyinhibitstheabilityofcellclonalformation[1].ATM-IN-2(1-4μM,2days)enhancesthetherapeuticefficacyofIrinotecan(HY-16562)byexacerbatingG2/Mphasearrest,andpromotingapoptosis,andachievingsynergisticantiproliferativeeffectsinHCT116cells[1].ATM-IN-2(0.25-2μM,4h)significantlyinhibitsATMsignalingactivationinHCT116andSW620cells[1].CellCycleAnalysis[1]CellLine:HCT116cellsConcentration:1,2,4μMIncubationTime:2daysResult:Alonehadnosignificanteffectonthecellcycle.IncreasedtheG2/Mphasepopulationinaconcentration-dependentmanner1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEaccompaniedbyareductionintheG0/G1phasepopulation.co-treatedwithIrinotecan.ApoptosisAnalysis[1]CellLine:HCT116cellsConcentration:1,2,4μMIncubationTime:2daysResult:Thecombinedtreatmentgroupexhibitedsignificantlyhigherapoptosisratescomparedtomonotherapy.WesternBlotAnalysis[1]CellLine:HCT116andSW620cellsConcentration:0.5,1,2μMinHCT116cellsand0.25,0.5,1μMinSW620cellsIncubationTime:4hResult:ReducedthephosphorylationlevelsofATM-S1981andp53.ReducedtheaccumulationofγH2AX.体内研究ATM-IN-2(Compound25a)(15-30mg/kg,p.o.,for14-20days)exertssynergisticantitumoreffectsincancertherapywithIrinotecaninmicexenograftmodel[1].AnimalModel:XenograftmodelinducedbyHCT116orSW620cellsestablishedin6-weeksNOD-SCIDmice[1]Dosage:30mg/kgaloneand15and30mg/kgwith2mg/kgIrinotecaninHCT116model;45mg/kgwith2mg/kgIrinotecaninSW620modelAdministration:Oraladministration(p.o.),for14daysinHCT116modeland20daysforSW620modelResult:Demonstratedsuperiorantitumorathigh-dosecoadministrationwithIrinotecaninHCT116model.DemonstratedafavorablesafetyprofilewithlittlebodyweightlossobservedinHCT116model.Demonstratedadose-dependentenhancementofinhibitoryeffectsinSW620model.REFERENCESGuoT,etal.Discoveryof1H-Pyrrolo[2,3-b]pyridineDerivativesasHighlySelective,andOrallyAvailableATMInhibitorswithPotentInVivoAntitumorActivity.JMedChem.2025Jul10;68(13):13907-13934.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEMcePdfHeightCaution:Producthasnotbeenfullyvalidatedformed