Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIberdomideCat.No.:HY-101291CASNo.:1323403-33-3Synonyms:CC-220分?式:C??H??N?O?分?量:449.5作?靶點:LigandsforE3Ligase;Apoptosis;MolecularGlues作?通路:PROTAC;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(278.09mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2247mL11.1235mL22.2469mL5mM0.4449mL2.2247mL4.4494mL10mM0.2225mL1.1123mL2.2247mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.63mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.63mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.63mM);ClearsolutionBIOLOGICALACTIVITY?物活性Iberdomide(CC-220)?種?服有效的cereblon(CRBN)E3連接酶調(diào)節(jié)劑(CELMoD)，對cereblon結合親和?的IC50為~150nM。Iberdomide沙利度胺(HY-14658)的衍?物，具有抗腫瘤和免疫刺激活性。體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻?CellHostMicrobe.2020Mar.?NatCancer.2022May;3(5):595-613.?NatCommun.2022Sep10;13(1):5324.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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