BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets英文文献资料.docVIP

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BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets英文文献资料.doc

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BAY 11-7082 Is a Broad-Spectrum Inhibitor with Anti-Inflammatory Activity against Multiple Targets英文文献资料

HindawiPublishingCorporation MediatorsofIn?ammation Volume2012,ArticleID416036,11pages doi:10.1155/2012/416036 ResearchArticle BAY11-7082IsaBroad-SpectrumInhibitorwith Anti-In?ammatoryActivityagainstMultipleTargets JaehwiLee, ManHeeRhee, EunjiKim, andJaeYoulCho 1 2 3 3 1 2 CollegeofPharmacy,Chung-AngUniversity,Seoul156-756,RepublicofKorea LaboratoryofPhysiologyCellSignaling,CollegeofVeterinaryMedicine,KyungpookNationalUniversity, Daegu702-701,RepublicofKorea 3 DepartmentofGeneticEngineering,SungkyunkwanUniversity,Suwon440-746,RepublicofKorea CorrespondenceshouldbeaddressedtoManHeeRhee,rheemh@knu.ac.krandJaeYoulCho,jaecho@ Received6March2012;Revised5April2012;Accepted5April2012 AcademicEditor:GiamilaFantuzzi Copyright?2012JaehwiLeeetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. BAY11-7082(BAY)isaninhibitorofκBkinase(IKK)thathaspharmacologicalactivitiesthatincludeanticancer,neuroprotective, and anti-in?ammatory e?ects. In this study, BAY-pharmacological target pathways were further characterized to determine howthiscompoundsimultaneouslysuppressesvariousresponses.Primaryandcancerous(RAW264.7cells)macrophageswere activatedbylipopolysaccharide,aligandoftoll-likereceptor4.Asreportedpreviously,BAYstronglysuppressedtheproduction ofnitricoxide,prostaglandinE2,andtumornecrosisfactor-αandreducedthetranslocationofp65,majorsubunitofnuclear factor-κB,anditsupstreamsignalingeventssuchasphosphorylationofIκBα,IKK,andAkt.Inaddition,BAYalsosuppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1byinhibitingthephosphorylationoractivationofextracellularsignal-relatedkinase,p38,TANK-bindingprotein, andJanuskinase-2.ThesedatastronglysuggestthatBAYisaninhibitorwithmultipletargetsandcouldserveasaleadcompou