{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:06:32Z","timestamp":1781247992649,"version":"3.54.1"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21672093"],"award-info":[{"award-number":["21672093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.bmc.2022.117152","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T11:42:45Z","timestamp":1672314165000},"page":"117152","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Design, synthesis, and biological evaluation of quinoxalinone derivatives as potent BRD4 inhibitors"],"prefix":"10.1016","volume":"78","author":[{"given":"Kai-Yan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Hang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Tao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Wu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2022.117152_b0005","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/20974","article-title":"Structure and ligand of a histone acetyltransferase bromodomain","volume":"399","author":"Dhalluin","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.bmc.2022.117152_b0010","doi-asserted-by":"crossref","unstructured":"P. Tang, J. Zhang, J. Liu, C.-M. Chiang, L.J.J.o.m.c. Ouyang. Targeting bromodomain and extraterminal proteins for drug discovery: from current progress to technological development, J. Med. Chem. 2021;64:2419\u22122435.","DOI":"10.1021\/acs.jmedchem.0c01487"},{"key":"10.1016\/j.bmc.2022.117152_b0015","doi-asserted-by":"crossref","unstructured":"F. Jiang, Q. Hu, Z. Zhang, H. Li, H. Li, D. Zhang, H. Li, Y. Ma, J. Xu, H.J.J.o.M.C. Chen. Discovery of benzo [cd] indol-2 (1 H)-ones and pyrrolo [4, 3, 2-de] quinolin-2 (1 H)-ones as bromodomain and extra-terminal domain (BET) inhibitors with selectivity for the first bromodomain with potential high efficiency against acute gouty arthritis, J. Med. Chem. 2019;62:11080\u221211107.","DOI":"10.1021\/acs.jmedchem.9b01010"},{"key":"10.1016\/j.bmc.2022.117152_b0020","doi-asserted-by":"crossref","unstructured":"C.-M.J.F.b.r. Chiang. Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4, F1000 Biology Reports 2009;1:e98.","DOI":"10.3410\/B1-98"},{"key":"10.1016\/j.bmc.2022.117152_b0025","doi-asserted-by":"crossref","unstructured":"A. Dey, F. Chitsaz, A. Abbasi, T. Misteli, K.J.P.o.t.N.A.o.S. Ozato. The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis, P. Natl. Acad. Sci. USA. 2003;100:8758\u22128763.","DOI":"10.1073\/pnas.1433065100"},{"key":"10.1016\/j.bmc.2022.117152_b0030","doi-asserted-by":"crossref","unstructured":"D.A. Bisgrove, T. Mahmoudi, P. Henklein, E.J.P.o.t.N.A.o.S. Verdin. Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription, Proc. Natl. Acad. Sci. USA. 2007;104:13690\u221213695.","DOI":"10.1073\/pnas.0705053104"},{"key":"10.1016\/j.bmc.2022.117152_b0035","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.molcel.2012.12.006","article-title":"C.-M.J.M.c. Chiang. Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting","volume":"49","author":"Wu","year":"2013","journal-title":"Molecular Cell"},{"key":"10.1016\/j.bmc.2022.117152_b0040","doi-asserted-by":"crossref","first-page":"13457","DOI":"10.1073\/pnas.1919507117","article-title":"MYC protein stability is negatively regulated by BRD4","volume":"117","author":"Devaiah","year":"2020","journal-title":"Proceedings of the National academy of Sciences of the United States of America"},{"key":"10.1016\/j.bmc.2022.117152_b0045","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1126\/science.aat6664","article-title":"BRD4 and MYC\u2014clarifying regulatory specificity","volume":"360","author":"Sab\u00f2","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.bmc.2022.117152_b0050","doi-asserted-by":"crossref","unstructured":"S.-Y. Wu, D.S. Nin, A.-Y. Lee, S. Simanski, T. Kodadek, C.-M.J.C.r. Chiang. BRD4 phosphorylation regulates HPV E2-mediated viral transcription, origin replication, and cellular MMP-9 expression, Cell Rep. 2016;16:1733\u22121748.","DOI":"10.1016\/j.celrep.2016.07.001"},{"key":"10.1016\/j.bmc.2022.117152_b0055","doi-asserted-by":"crossref","unstructured":"B. Huang, X.-D. Yang, M.-M. Zhou, K. Ozato, L.-F.J.M. Chen, c. biology. Brd4 coactivates transcriptional activation of NF-\u03baB via specific binding to acetylated RelA, Mol. Cell Biol. 2009;29:1375\u22121387.","DOI":"10.1128\/MCB.01365-08"},{"key":"10.1016\/j.bmc.2022.117152_b0060","doi-asserted-by":"crossref","unstructured":"S. Gokani, L.K.J.E.J.o.P. Bhatt. Bromodomains: A novel target for the anticancer therapy, Eur. J. Pharmacol. 2021;911:e174523.","DOI":"10.1016\/j.ejphar.2021.174523"},{"key":"10.1016\/j.bmc.2022.117152_b0065","doi-asserted-by":"crossref","unstructured":"P.C. Borck, L.-W. Guo, J.J.C.r. Plutzky. BET epigenetic reader proteins in cardiovascular transcriptional programs, Circ. Res. 2020;126:1190\u22121208.","DOI":"10.1161\/CIRCRESAHA.120.315929"},{"key":"10.1016\/j.bmc.2022.117152_b0070","doi-asserted-by":"crossref","first-page":"4829","DOI":"10.1002\/jcp.30225","article-title":"X.L.J.J.o.C.P. Zheng. Bromodomain-containing protein 4 and its role in cardiovascular diseases","volume":"236","author":"Li","year":"2021","journal-title":"Journal of Cellular Physiology"},{"key":"10.1016\/j.bmc.2022.117152_b0075","doi-asserted-by":"crossref","unstructured":"D.J.N.R.C. Ummarino. BRD4 inhibition slows HF progression, Nat. Rev. Cardiol. 2017;14:383\u2212383.","DOI":"10.1038\/nrcardio.2017.86"},{"key":"10.1016\/j.bmc.2022.117152_b0080","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/s42255-020-0261-2","article-title":"Fructose stimulated de novo lipogenesis is promoted by inflammation","volume":"2","author":"Todoric","year":"2020","journal-title":"Nat. Metab."},{"key":"10.1016\/j.bmc.2022.117152_b0085","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.3390\/biomedicines6010016","article-title":"BET family protein BRD4: An emerging actor in NF\u03baB signaling in inflammation and cancer","volume":"6","author":"Hajmirza","year":"2018","journal-title":"Biomedicines"},{"key":"10.1016\/j.bmc.2022.117152_b0090","doi-asserted-by":"crossref","unstructured":"N. Wang, R. Wu, D. Tang, R.J.S.t. Kang, t. therapy. The BET family in immunity and disease, Signal Transduct. Tar. 2021;6:1\u221222.","DOI":"10.1038\/s41392-020-00384-4"},{"key":"10.1016\/j.bmc.2022.117152_b0095","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nature Reviews Disease Primers"},{"key":"10.1016\/j.bmc.2022.117152_b0100","first-page":"1","article-title":"BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4","volume":"11","author":"Choi","year":"2021","journal-title":"Sci. Rep-Uk."},{"key":"10.1016\/j.bmc.2022.117152_b0105","first-page":"36","article-title":"Shi, pharmacology. BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma","volume":"28","author":"Zhang","year":"2015","journal-title":"Int. J. Immunopath. Ph."},{"key":"10.1016\/j.bmc.2022.117152_b0110","unstructured":"K.F. McDaniel, L. Wang, T. Soltwedel, S.D. Fidanze, L.A. Hasvold, D. Liu, R.A. Mantei, J.K. Pratt, G.S. Sheppard, M.H.J.J.o.m.c. Bui. Discovery of N-(4-(2, 4-Difluorophenoxy)-3-(6-methyl-7-oxo-6, 7-dihydro-1 H-pyrrolo [2, 3-c] pyridin-4-yl) phenyl) ethanesulfonamide (ABBV-075\/Mivebresib), a potent and orally available bromodomain and extraterminal domain (BET) family bromodomain inhibitor, J. Med. Chem. 2017;60:8369\u22128384."},{"key":"10.1016\/j.bmc.2022.117152_b0115","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1158\/1078-0432.CCR-19-0578","article-title":"First-in-human study of mivebresib (ABBV-075), an oral pan-inhibitor of bromodomain and extra terminal proteins, in patients with relapsed\/refractory solid tumors","volume":"25","author":"Piha-Paul","year":"2019","journal-title":"Clinical Cancer Research"},{"key":"10.1016\/j.bmc.2022.117152_b0120","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1002\/cncr.33590","article-title":"A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed\/refractory acute myeloid leukemia","volume":"127","author":"Borthakur","year":"2021","journal-title":"Cancer"},{"key":"10.1016\/j.bmc.2022.117152_b0125","doi-asserted-by":"crossref","first-page":"e112780","DOI":"10.1016\/j.ejmech.2020.112780","article-title":"Design, synthesis and biological evaluation of indole-2-one derivatives as potent BRD4 inhibitors","volume":"208","author":"Xu","year":"2020","journal-title":"European Journal of Medicinal Chemistry"},{"key":"10.1016\/j.bmc.2022.117152_b0130","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.1016\/j.bmcl.2016.09.075","article-title":"Design, synthesis and structure\u2013activity relationships of novel phenylalanine-based amino acids as kainate receptors ligands","volume":"26","author":"Szyma\u0144ska","year":"2016","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"10.1016\/j.bmc.2022.117152_b0135","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1080\/00397910500213880","article-title":"W.J.S.c. Xu. Novel approach to 3-methyl-1H-quinoxalin-2-ones","volume":"35","author":"Li","year":"2005","journal-title":"Synthetic Commun."},{"key":"10.1016\/j.bmc.2022.117152_b0140","doi-asserted-by":"crossref","unstructured":"J. Chen, Y. Li, J. Zhang, M. Zhang, A. Wei, H. Liu, Z. Xie, W. Ren, W. Duan, Z.J.E.J.o.M.C. Zhang. Discovery of selective HDAC\/BRD4 dual inhibitors as epigenetic probes, Eur. J. Med. Chem. 2021;209:e112868.","DOI":"10.1016\/j.ejmech.2020.112868"},{"key":"10.1016\/j.bmc.2022.117152_b0145","doi-asserted-by":"crossref","first-page":"e106117","DOI":"10.1016\/j.bioorg.2022.106117","article-title":"Design, synthesis and biological evaluation of coumarin derivatives as potential BRD4 inhibitors","volume":"128","author":"Cui","year":"2022","journal-title":"Bioorganic Chemistry"},{"key":"10.1016\/j.bmc.2022.117152_b0150","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1158\/0008-5472.CAN-16-1793","article-title":"Preclinical characterization of BET family bromodomain inhibitor ABBV-075 suggests combination therapeutic strategies ABBV-075 induces apoptosis and exhibits synergy with ABT-199","volume":"77","author":"Bui","year":"2017","journal-title":"Cancer Research"},{"key":"10.1016\/j.bmc.2022.117152_b0155","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1021\/acs.jmedchem.7b01666","article-title":"Discovery of tetrahydroquinoxalines as bromodomain and extra-terminal domain (BET) inhibitors with selectivity for the second bromodomain","volume":"61","author":"Law","year":"2018","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.bmc.2022.117152_b0160","doi-asserted-by":"crossref","first-page":"8642","DOI":"10.1021\/acs.jmedchem.9b01094","article-title":"Structure-Based discovery and development of a series of potent and selective bromodomain and extra-terminal protein inhibitors","volume":"62","author":"Hu","year":"2019","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.bmc.2022.117152_b0165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-021-03494-w","article-title":"Acacetin inhibits invasion, migration and TGF-\u03b21-induced EMT of gastric cancer cells through the PI3K\/Akt\/Snail pathway","volume":"22","author":"Zhang","year":"2022","journal-title":"BMC. Complement Med. Ther."},{"key":"10.1016\/j.bmc.2022.117152_b0170","doi-asserted-by":"crossref","unstructured":"S. Lamouille, J. Xu, R.J.N.r.M.c.b. Derynck. Molecular mechanisms of epithelial\u2013mesenchymal transition, Nat. Rev. Mol. Cell Biol. 2014;15:178\u2212196.","DOI":"10.1038\/nrm3758"},{"key":"10.1016\/j.bmc.2022.117152_b0175","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrc3647","article-title":"Beyond E-cadherin: roles of other cadherin superfamily members in cancer","volume":"14","author":"Van Roy","year":"2014","journal-title":"Nature Reviews. Cancer"},{"key":"10.1016\/j.bmc.2022.117152_b0180","doi-asserted-by":"crossref","unstructured":"A.R. Brasier, D. Qiao, Y.J.F.i.P. Zhao. The hexosamine biosynthetic pathway links innate inflammation with epithelial-mesenchymal plasticity in airway remodeling, Mol. Cancer 2021;12: e808735.","DOI":"10.3389\/fphar.2021.808735"},{"key":"10.1016\/j.bmc.2022.117152_b0185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-021-01424-5","article-title":"The role of distinct BRD4 isoforms and their contribution to high-grade serous ovarian carcinoma pathogenesis","volume":"20","author":"Drumond-Bock","year":"2021","journal-title":"Molecular Cancer"},{"key":"10.1016\/j.bmc.2022.117152_b0190","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nature10509","article-title":"Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia","volume":"478","author":"Dawson","year":"2011","journal-title":"Nature"}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622005454?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089622005454?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:21:31Z","timestamp":1760836891000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089622005454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":38,"alternative-id":["S0968089622005454"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2022.117152","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis, and biological evaluation of quinoxalinone derivatives as potent BRD4 inhibitors","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2022.117152","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"117152"}}