Iberdomide-CC-220-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEIberdomideCat.No.:HY-101291CASNo.:1323403-33-3Synonyms:CC-220分⼦式:C₂₅H₂₇N₃O₅分⼦量:449.5作⽤靶点:LigandsforE3Ligase;Apoptosis;MolecularGlues作⽤通路:PROTAC;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(278.09mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2247mL11.1235mL22.2469mL5mM0.4449mL2.2247mL4.4494mL10mM0.2225mL1.1123mL2.2247mL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。-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。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.63mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.63mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.63mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Iberdomide(CC-220)⼀种⼝服有效的cereblon(CRBN)E3连接酶调节剂(CELMoD)，对cereblon结合亲和⼒的IC50为~150nM。Iberdomide沙利度胺(HY-14658)的衍⽣物，具有抗肿瘤和免疫刺激活性。体外研究Iberdomide(CC-220;0.01,0.1,1,10μM;72-96hrs)hasantiproliferativeeffectsinapanelofmultiplemyeloma(MM)celllines(EJM,H929,KMS11,KMS128M,KMS12PE,MM1.S,MM1.R,RPM-8226,U266cells)acrossarangeofconcentrations[1].Iberdomide(0.1μM;96hrs)inducesapoptosisinallMMcelllines[1].Iberdomide(0.1μM;24,48,72hrs)resultsintime-dependentincreasesinG0/G1andsub-G1cellcyclefractionsonH929cells[1].IberdomideleadstorapidAiolosdepletionintheKMS12BMline[1].Iberdomide(0.1μM)displayssomeanti-proliferativeactivityintwoofthePomalidomide-resistant(PR)lineswithcereblonmutations(EJM/PRandH929/PR)alongwithdecreasedlevelsofcereblonprotein[1].Iberdomide(0.1-1000nM;72hrs)equallyinducesPBMC-mediatedkillingofbothparentalMM1.ScellsandMM1.S/PRcells[1].体内研究Iberdomide(CC-220;10mg/kg;oralgavage)after6or24hourscauseshigherhCRBNexpressioninhC343splenocytescorrelatedtodeeperIKZF1/3downregulationinWT(C57BL/6),hC123,or-343,(representingtwodifferenttransgenicfounderlinesexpressinghCRBN)andmCrbn-/-mice[2].PROTOCOLKinaseAssay[1]IberdomideisdissolvedinDMSO.Intheassay,60nM6Xhis-taggedCRBN-DDB1iscombinedwith30nMcy5-conjugatedcereblonmodulatorand3nMLanthaScreenEu-anti-HisTagantibodyin20mMHEPESpH7,150mMNaCl,0.005%Tween-20assaybuffer.FRETisobservedbyexcitingat340nmandmonitoringemissionat615nmand665nm,andFRETefficiencyisdeterminedbytheratioofFRETtonon-FRETemission.Competingcereblonmodulatingcompound(Iberdomide)orDMSOcarrieristitratedandincubatedfor10minbeforescanning[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellHostMicrobe.2020Mar.•NatCancer.2022May;3(5):595-613.•NatCommun.2022Sep10;13(1):5324.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•BloodCancerJ.2019Feb11;9(2):19.•CellChemBiol.2020Jul16;27(7):866-876.e8.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ChadCBjorklund,etal.Iberdomide(CC-220)isapotentcereblonE3ligasemodulatorwithantitumorandimmunostimulatoryactivitiesinlenalidomide-andpomalidomide-resistantmultiplemyelomacellswithdysregulatedCRBN.Leukemia.2020Apr;34(4):1197-1201.[2].ErinWMeermeier,etal.TumorburdenlimitsbispecificantibodyefficacythroughTcellexhaustionavertedbyconcurrentcytotoxictherapy.BloodCancerDiscov.2021Jul;2(4):354-369.McePdfHeightCa