Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEMGD-22Cat.No.:HY-175502CASNo.:2991818-12-1分子式:C??H??N?O?分子量:577.68作用靶點:MolecularGlues;IKZFFamily;Apoptosis作用通路:PROTAC;Immunology/Inflammation;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性MGD-22，一種分子膠，是一種口服活性的IKZF1/2/3降解劑，其DC50值分別為8.33nM、9.91nM和5.74nM。MGD-22對多種血液癌癥細胞表現(xiàn)出極強的抗增殖活性。MGD-22誘導癌癥細胞凋亡(apoptosis)。MGD-22在NCI-H929異種移植瘤或WSU-DLCL-2異種移植瘤的小鼠中展示出強大的抗腫瘤效能。MGD-22可用于研究血液癌癥，包括多發(fā)性骨髓瘤(MM)、急性髓系白血病(AML)和彌漫大B細胞淋巴瘤(DLBCL)[1]。IC50&TargetIKZF1IKZF2IKZF38.33nM(DC50)9.91nM(DC50)5.74nM(DC50)體外研究MGD-22(0-100μM,96h)exhibitsextremelypotentanti-proliferativeactivityagainstmultiplemyeloma(MM)celllinesincludingNCI-H929(IC50=7.93nM),RPMI-8226(IC50=83.2nM),OPM-2(IC50=7.87nM);acutemyeloidleukemia(AML)celllinesincludingMV-4-11(IC50=5.38±0.43nM),U937(IC50=15.1nM),MOLM-13(IC50=196nM),KG-1(IC50=78.9nM),Skm-1(IC50=218nM),MUTZ-1(IC50=148nM);diffuselargeB-celllymphoma(DLBCL)celllinesincludingWSU-DLCL-2(IC50=8.99nM),Ocl-Ly3(IC50=95.3nM),SU-DHL-4(IC50=452nM),TMD8(IC50=87.7nM),U2932(IC50=8.17nM);whileshowingnegligibleactivityagainstnormalperipheralbloodmononuclearcells(PBMCs)andprimaryBcells(IC50>33μM[1].MGD-22(0.01-10μM,72h)inducesdose-dependentapoptosisinNCI-H929andMV-4-11cells[1].MGD-22(0.001-1000nM,24h)selectivelyinducesrobustdegradationofIKZF1/2/3inHEK293TcellsengineeredwithIKZF1/2/3-HiBittags,withDC50valuesof8.33nM(IKZF1),9.91nM(IKZF2),and5.74nM(IKZF3),andmaximaldegradation(Dmax)of94.33%,91.58%,and92.26%respectively[1].MGD-22(1μM,24h)promotestheformationofaternarycomplexbetweenIKZF1/2/3andCRBNinNCI-H929cells[1].1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEApoptosisAnalysis[1]CellLine:NCI-H929andMV-4-11cellsConcentration:0.01,0.1,1,10μMIncubationTime:72hResult:Induceddose-dependentapoptosisinNCI-H929andMV-4-11cells.體內(nèi)研究MGD-22(3-10mg/kg,p.o.,oncedaily,14days)demonstratespotentanti-tumorefficacyinNOD/SCIDmicebearingNCI-H929xenografts[1].MGD-22(5mg/kg,p.o.,oncedaily,36days)combinedwithIbrutinib(HY-10997)orVenetoclax(HY-15531)for36daysexhibitssynergisticanti-tumorefficacyinNOD/SCIDmicebearingWSU-DLCL-2xenografts[1].AnimalModel:NCI-H929cells(7.5×106)weresubcutaneouslyinoculatedintobothsidesofthedorsalbackof6-week-oldNOD/SCIDmicetoestablishthemultiplemyeloma(MM)xenograftmodel[1]Dosage:3,10mg/kgAdministration:p.o.,oncedaily,14daysResult:Exhibitedsuperioranti-tumorefficacy.Causedonlyminorbodyweightreductionthroughoutthetreatmentperiod.ReducedKi67-positiveproliferativecellsandincreasescleaved-caspase-3-positiveapoptoticcells.DegradedIKZF1/2/3proteinsinNCI-H929xenografttumortissues.AnimalModel:WSU-DLCL-2cells(1×107)weresubcutaneouslyimplantedintobothsidesofthedorsalbackof6-week-oldNOD/SCIDmicetoconstructthediffuselargeB-celllymphoma(DLBCL)xenograftmodel[1]Dosage:5mg/kgcombinedwithIbrutinib(HY-10997)(10mg/kg,p.o.,oncedaily)orVenetoclax(HY-15531)(30mg/kg,p.o.,oncedaily)Administration:p.o.,oncedaily,36daysResult:Demonstratedanti-tumorefficacyinNOD/SCIDmicebearingWSU-DLCL-2xenografts.ImprovedthesurvivalrateofNOD/SCIDmice.Maintainedstablebodyweight.REFERENCES[1].WeiT,etal.DiscoveryofNovelPotentTripleIKZF1/2/3DegradersfortheTreatmentofHematologicalCancers.JMedChem.2025Aug2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemE14;68(15):16237-16259.McePdfHeightCaution:P