
Description | Avadomide(CC-122),anewchemicalentitytermedpleiotropicpathwaymodifier,isanovelagentforDiffuselargeB-celllymphoma(DLBCL)withantitumorandimmunomodulatoryactivity.Itsmoleculartargetistheproteincereblon(CRBN),asubstratereceptorofthecullinringE3ubiquitinligasecomplexCRL4CRBN. | ||||||||
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Invitro | CC-122isanovelagentforDLBCLwithantitumorandimmunomodulatoryactivity.InDLBCLcelllines,ItbindsCRBNandinducesdegradationorshorthairpinRNA-mediatedknockdownofAiolosandIkaroswhichcorrelateswithincreasedtranscriptionofinterferon(IFN)-stimulatedgenesindependentofIFN-α,-β,and-γproductionand/orsecretionandresultsinapoptosisinbothactivatedB-cell(ABC)andgerminalcenterB-cellDLBCLcelllines.CRBNisthemoleculartargetofCC-122,CC-122bindingtoCRBNrecruitsAiolos/IkarostoCRL4CRBN,andE3ligaseenzymaticactivityisnecessaryforubiquitinationofAiolosandIkarosandthustheirproteasomaldegradationinducedbyCC-122.CC-122inducesIFN-regulatedproteinsanditsmediatedeffectsontheIFNpathwayisindependentofautocrinetypeIandIIIFNsecretionandsignaling[1]. | ||||||||
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