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Lactam-based HDAC inhibitors for anticancer chemotherapy: Restoration of RUNX3 by posttranslational modification and epigenetic control

DC Field Value Language
dc.contributor.author황기철-
dc.date.accessioned2015-01-06T16:41:55Z-
dc.date.available2015-01-06T16:41:55Z-
dc.date.issued2014-
dc.identifier.issn1860-7179-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/98593-
dc.description.abstractExpression and stability of the tumor suppressor runt-related transcription factor 3 (RUNX3) are regulated by histone deacetylase (HDAC). HDAC inhibition alters epigenetic and posttranslational stability of RUNX3, leading to tumor suppression. However, HDAC inhibitors can nonselectively alter global gene expression through chromatin remodeling. Thus, lactam-based HDAC inhibitors were screened to identify potent protein stabilizers that maintain RUNX3 stability by acetylation. RUNX activity and HDAC inhibition were determined for 111 lactam-based analogues through a cell-based RUNX activation and HDAC inhibition assay. 3-[1-(4-Bromobenzyl)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-N-hydroxypropanamide (11-8) significantly increased RUNX3 acetylation and stability with relatively low RUNX3 mRNA expression and HDAC inhibitory activity. This compound showed significant antitumor effects, which were stronger than SAHA, in an MKN28 xenograft model. Thus, we propose a novel strategy, in which HDAC inhibitors serve as antitumor chemotherapeutic agents that selectively target epigenetic regulation and protein stability of RUNX3.-
dc.description.statementOfResponsibilityopen-
dc.format.extent649~656-
dc.relation.isPartOfCHEMMEDCHEM-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAntineoplastic Agents/chemical synthesis-
dc.subject.MESHAntineoplastic Agents/chemistry-
dc.subject.MESHAntineoplastic Agents/pharmacology*-
dc.subject.MESHCell Proliferation/drug effects-
dc.subject.MESHCore Binding Factor Alpha 3 Subunit/antagonists & inhibitors-
dc.subject.MESHCore Binding Factor Alpha 3 Subunit/chemistry-
dc.subject.MESHCore Binding Factor Alpha 3 Subunit/genetics-
dc.subject.MESHCore Binding Factor Alpha 3 Subunit/metabolism*-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHEpigenesis, Genetic/drug effects*-
dc.subject.MESHGene Expression Profiling-
dc.subject.MESHHistone Deacetylase Inhibitors/chemical synthesis-
dc.subject.MESHHistone Deacetylase Inhibitors/chemistry-
dc.subject.MESHHistone Deacetylase Inhibitors/pharmacology*-
dc.subject.MESHHistone Deacetylases/metabolism*-
dc.subject.MESHLactams/chemical synthesis-
dc.subject.MESHLactams/chemistry-
dc.subject.MESHLactams/pharmacology*-
dc.subject.MESHMice-
dc.subject.MESHMice, Nude-
dc.subject.MESHModels, Molecular-
dc.subject.MESHMolecular Conformation-
dc.subject.MESHNeoplasms, Experimental/drug therapy*-
dc.subject.MESHNeoplasms, Experimental/metabolism-
dc.subject.MESHNeoplasms, Experimental/pathology-
dc.subject.MESHProtein Stability/drug effects-
dc.subject.MESHRNA, Messenger/antagonists & inhibitors-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHStructure-Activity Relationship-
dc.subject.MESHXenograft Model Antitumor Assays-
dc.titleLactam-based HDAC inhibitors for anticancer chemotherapy: Restoration of RUNX3 by posttranslational modification and epigenetic control-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Life Science (의생명과학부)-
dc.contributor.googleauthorMisun Cho-
dc.contributor.googleauthorEunhyun Choi-
dc.contributor.googleauthorJae Hyun Kim-
dc.contributor.googleauthorHwan Kim-
dc.contributor.googleauthorHwan Mook Kim-
dc.contributor.googleauthorJang Ik Lee-
dc.contributor.googleauthorKi-Chul Hwang-
dc.contributor.googleauthorHyun-Jung Kim-
dc.contributor.googleauthorGyoonhee Han-
dc.identifier.doi10.1002/cmdc.201300393-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA04456-
dc.relation.journalcodeJ00517-
dc.identifier.eissn1860-7187-
dc.identifier.pmid24376239-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1002/cmdc.201300393/abstract-
dc.subject.keyworddrug discovery-
dc.subject.keywordhistone deacetylase-
dc.subject.keywordinhibitors-
dc.subject.keywordlactam-
dc.subject.keywordrunt-related transcription factor 3-
dc.contributor.alternativeNameHwang, Ki Chul-
dc.contributor.affiliatedAuthorHwang, Ki Chul-
dc.rights.accessRightsfree-
dc.citation.volume9-
dc.citation.number3-
dc.citation.startPage649-
dc.citation.endPage656-
dc.identifier.bibliographicCitationCHEMMEDCHEM, Vol.9(3) : 649-656, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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