PROTAC-EML4-ALK-Degrader-2-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPROTACEML4-ALKDegrader-2Cat.No.:HY-180972CASNo.:2417174-28-6分⼦式:C₅₂H₆₆ClN₉O₁₁S分⼦量:1060.65作⽤靶点:PROTACs;Anaplasticlymphomakinase(ALK)作⽤通路:PROTAC;ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PROTACEML4-ALKDegrader-2⼀种EML4-ALKPROTAC降解。PROTACEML4-ALKDegrader-2对ALK表现出强效的选择性抑制活性，其IC50为1.6nM。PROTACEML4-ALK对IGF1R、INSR、FLT3和FGFR2表现出选择性。PROTACEML4-ALKDegrader-2在体外和体内均具有抗癌活性。PROTACEML4-ALKDegrader-2可⽤于⾮⼩细胞肺癌(NSLC)，肺癌和宫颈癌的研究[1][2]。IC50&TargetEML4-ALK体外研究PROTACEML4-ALKDegrader-2(compoundB3)(72h)showsdonotincreasethetoxicitytonormalcellsinnormalhumanlivercelllineLO2andshowsanti-proliferationeffectinH3122,H2228,H1299.A549andHeLacellswithIC50sof0.3,0.9,2.84,1.6and1.18μM,respectively[1].PROTACEML4-ALKDegrader-2(0-50nM,0-32h)decreasesthecellularlevelsofALKfusionproteinsinaconcentration-andtime-dependentmannerinH3122cells[1].PROTACEML4-ALKDegrader-2(10-500nM)showshighselectivitytoALK,maintainingmoderateinhibitionactivitytoIGF1RandINSR,andnotinducethedegradationofIGF1RandINSR[1].PROTACEML4-ALKDegrader-2iseffectiveagainstALK-resistantmutations,withitsanti-resistanceactivityspectrumbeinglimitedtoBaF3-ALK-L1196MandBaF3-ALK-G1202Rcells,exhibitingmarginallysuperioractivitytoLDK378intargetingBaF3-ALK-L1196Mcells[1].WesternBlotAnalysis[1]CellLine:H3122cellsConcentration:0,1,5,10,20,50and100nM1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:0,4,8,16,24and32hResult:DegradedALKinadosedependentmannerfor8h;effectivelydegradedALKat50nMfor8h;degradedalltheALKproteinat200nM.Achievedamount(>80%)ofEML4-ALKdegradationafter16htreatmentat100nM.NotobservedmaximumdegradationofEML4-ALKdegradationuntil24hat100nM.Inhibitedp-ALKanddownregulatedthelevelofp-STAT3after24hat100nM.InducedALKdegradationinaconcentrationdependentmannerafter24h.AchievedmaximumdegradationofEML4-ALKdegradationat50nM.Downregulatedthelevelofp-ALKandp-STAT3inaconcentrationdependentmannerafter24h.体内研究PROTACEML4-ALKDegrader-2(compoundB3)(25-50mg/kg,o.p.,oncedailyfor15days)inhibitsgrowthofxenografttumorsinadose-dependentmannerwithsafetyprofileinH3122xenograftmice[1].AnimalModel:H3122cells(5x106)induced-femaleBALB/cnudemice(6-7weeks)(18-22g)[1]Dosage:25,50mg/kgAdministration:o.p.,oncedailyfor15daysResult:Observedtumorgrowthinhibitions(TGIs)of37%and48%atdoseof25mg/kgand50mg/kg,respectively.Didnotcausesignificantweightlossandtoxicity.REFERENCES[1].YanG,etal.DiscoveryofaPROTACtargetingALKwithinvivoactivity.EurJMedChem.2021Feb15;212:113150.[2].ChenX,etal.Mightymini-PROTACs:anemergingclassofdegraders.EurJMedChem.2026Jan5;301:118202.McePdfHeightCaution:Producthasnotbeenfullyvalidate