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Using a selective small-molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as regulatory factors for c-Myc. BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes. In experimental models of multiple myeloma, a Myc-dependent hematologic malignancy, JQ1 produces a potent antiproliferative effect associated with cell-cycle arrest and cellular senescence. Efficacy of JQ1 in three murine models of multiple myeloma establishes the therapeutic rationale for BET bromodomain inhibition in this disease and other malignancies characterized by pathologic activation of c-Myc.","is_dataset_classified":null,"base_score":7.962763930168115,"endowment":7.962763930168115,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21889194","pmcid":"PMC3187920","openalex_id":"https://openalex.org/W2120572492","authors":[],"funders":[{"funder_name":"NHGRI NIH HHS","grant_id":"R01 HG002668","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01CA46455","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA136671","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG020686","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA050947","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K08CA128972","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA133966","title":null},{"funder_name":"National Institutes of Health","grant_id":"5K08CA128972-03","title":"Selective Inhibition of HDAC6 in Cancer Therapy"},{"funder_name":"National Institutes of Health","grant_id":"1R01CA050947-01A1","title":"CHARACTERIZATION OF GROWTH FACTOR RESPONSIVE B CELLS"},{"funder_name":"National Institutes of Health","grant_id":"1R01HG002668-01","title":"Transcriptional Ragulatory Network in Living Cells"},{"funder_name":"National Institutes of Health","grant_id":"7R29CA046455-02","title":"STUDIES ON HUMAN DBL ONCOGENE PRODUCT"},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":13,"fwci":64.9608,"citation_percentile":0.99975854,"influential_citations":0,"citation_trend":[{"year":2012,"count":116},{"year":2013,"count":179},{"year":2014,"count":228},{"year":2015,"count":229},{"year":2016,"count":240},{"year":2017,"count":231},{"year":2018,"count":241},{"year":2019,"count":247},{"year":2020,"count":220},{"year":2021,"count":234},{"year":2022,"count":176},{"year":2023,"count":180},{"year":2024,"count":157},{"year":2025,"count":113},{"year":2026,"count":64}],"oa_status":"bronze","license":"Elsevier Non-Commercial","oa_locations":[{"url":"http://www.cell.com/article/S0092867411009433/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S0092867411009433/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867411009433?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867411009433?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.cell.2011.08.017","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21889194","host_type":"repository"},{"url":"https://repository.cshl.edu/id/eprint/15654/","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3187920","host_type":"repository"},{"url":"http://dx.doi.org/10.1016/j.cell.2011.08.017","host_type":""},{"url":"https://dx.doi.org/10.1016/j.cell.2011.08.017","host_type":""},{"url":"https://hdl.handle.net/1721.1/92489","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.cell.2011.08.017","host_type":""}],"fields_of_study":["Protein Degradation and Inhibitors","Multiple Myeloma Research and Treatments","Histone Deacetylase Inhibitors Research","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Antineoplastic Agents","Azepines","Benzodiazepines","Cell Line, Tumor","Disease Models, Animal","Drug Discovery","Humans","Mice","Multiple Myeloma","Nuclear Proteins","Protein Structure, Tertiary","Proto-Oncogene Proteins c-myc","Transcriptional Activation","Triazoles"],"mesh_terms":["Animals","Antineoplastic Agents","Azepines","Benzodiazepines","Disease Models, Animal","Humans","Multiple Myeloma","Nuclear Proteins","Triazoles","Transcriptional Activation","Proto-Oncogene Proteins c-myc","Protein Structure, Tertiary","Cell Line, Tumor","Mice","Drug Discovery"],"keywords":["Bromodomain","BRD4","BET inhibitor","Biology","Cancer research","Chromatin","Transcription factor","Coactivator","Downregulation and upregulation","Transcription (linguistics)","Proto-Oncogene Proteins c-myc","RNA polymerase II","Gene","Histone","Cell biology","Gene expression","Genetics","Promoter","Transcriptional Activation","Biochemistry, Genetics and Molecular Biology(all)","Nuclear Proteins","Antineoplastic Agents","Azepines","Triazoles","Protein Structure, Tertiary","Benzodiazepines","Disease Models, Animal","Mice","Cell Line, Tumor","Drug Discovery","Animals","Humans","Multiple Myeloma"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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