{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:07:33Z","timestamp":1790838453693,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012242","name":"Program of Shanghai Subject Chief Scientist","doi-asserted-by":"publisher","award":["22XD1425300"],"award-info":[{"award-number":["22XD1425300"]}],"id":[{"id":"10.13039\/501100012242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010954","name":"Qingdao National Laboratory for Marine Science and Technology","doi-asserted-by":"publisher","award":["No.2022QNLM030003-2"],"award-info":[{"award-number":["No.2022QNLM030003-2"]}],"id":[{"id":"10.13039\/501100010954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010954","name":"Qingdao National Laboratory for Marine Science and Technology","doi-asserted-by":"publisher","award":["2022QNLM030003-2"],"award-info":[{"award-number":["2022QNLM030003-2"]}],"id":[{"id":"10.13039\/501100010954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0210600"],"award-info":[{"award-number":["2022YFE0210600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173835"],"award-info":[{"award-number":["82173835"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.ejmech.2025.118489","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T07:38:28Z","timestamp":1765870708000},"page":"118489","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Discovery of CZL-077 as a potent, selective, and orally active p300\/CBP bromodomain inhibitor with improved in vivo antitumor efficacy"],"prefix":"10.1016","volume":"304","author":[{"given":"Zonglong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongyu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5957-6918","authenticated-orcid":false,"given":"Yingxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ejmech.2025.118489_bib1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nrm.2016.143","article-title":"Functions of bromodomain-containing proteins and their roles in homeostasis and cancer","volume":"18","author":"Fujisawa","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118489_bib2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrd4286","article-title":"Targeting bromodomains: epigenetic readers of lysine acetylation","volume":"13","author":"Filippakopoulos","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118489_bib3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.cell.2012.02.013","article-title":"Histone recognition and large-scale structural analysis of the human bromodomain family","volume":"149","author":"Filippakopoulos","year":"2012","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.ejmech.2025.118489_bib4","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/cr500452k","article-title":"Protein lysine acetylation by p300\/CBP","volume":"115","author":"Dancy","year":"2015","journal-title":"Chem. Rev."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118489_bib5","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0092-8674(00)82001-2","article-title":"The transcriptional coactivators p300 and CBP are histone acetyltransferases","volume":"87","author":"Ogryzko","year":"1996","journal-title":"Cell"},{"issue":"6610","key":"10.1016\/j.ejmech.2025.118489_bib6","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/384641a0","article-title":"The CBP co-activator is a histone acetyltransferase","volume":"384","author":"Bannister","year":"1996","journal-title":"Nature"},{"issue":"6595","key":"10.1016\/j.ejmech.2025.118489_bib7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/383099a0","article-title":"Role of CBP\/P300 in nuclear receptor signalling","volume":"383","author":"Chakravarti","year":"1996","journal-title":"Nature"},{"issue":"22","key":"10.1016\/j.ejmech.2025.118489_bib8","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2022112012","article-title":"CBP\/p300 and HDAC activities regulate H3K27 acetylation dynamics and zygotic genome activation in mouse preimplantation embryos","volume":"41","author":"Wang","year":"2022","journal-title":"EMBO J."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118489_bib9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cell.2018.04.033","article-title":"Time-resolved analysis reveals rapid dynamics and broad scope of the CBP\/p300 acetylome","volume":"174","author":"Weinert","year":"2018","journal-title":"Cell"},{"issue":"5","key":"10.1016\/j.ejmech.2025.118489_bib10","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.molcel.2022.01.024","article-title":"The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation","volume":"82","author":"Miao","year":"2022","journal-title":"Mol Cell"},{"issue":"11","key":"10.1016\/j.ejmech.2025.118489_bib11","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.7150\/thno.73223","article-title":"Histone acetyltransferases CBP\/p300 in tumorigenesis and CBP\/p300 inhibitors as promising novel anticancer agents","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"issue":"24","key":"10.1016\/j.ejmech.2025.118489_bib12","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1038\/sj.onc.1207118","article-title":"p300\/CBP and cancer","volume":"23","author":"Iyer","year":"2004","journal-title":"Oncogene"},{"issue":"22","key":"10.1016\/j.ejmech.2025.118489_bib13","first-page":"7638","article-title":"p300 in prostate cancer proliferation and progression","volume":"63","author":"Debes","year":"2003"},{"key":"10.1016\/j.ejmech.2025.118489_bib14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/978-0-387-69080-3_54","article-title":"The role of the transcriptional coactivator p300 in prostate cancer progression","volume":"617","author":"Heemers","year":"2008","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ejmech.2025.118489_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2023.11.001","article-title":"Therapeutic targeting of EP300\/CBP by bromodomain inhibition in hematologic malignancies","author":"Nicosia","year":"2023","journal-title":"Cancer Cell"},{"issue":"5","key":"10.1016\/j.ejmech.2025.118489_bib16","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1158\/2159-8290.CD-20-0751","article-title":"Targeting the p300\/CBP axis in lethal prostate cancer","volume":"11","author":"Welti","year":"2021","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2025.118489_bib17","article-title":"Bromodomain inhibition of the transcriptional coactivators CBP\/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma","volume":"5","author":"Conery","year":"2016","journal-title":"eLife"},{"issue":"6","key":"10.1016\/j.ejmech.2025.118489_bib18","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1002\/hep.30544","article-title":"Aberrant super-enhancer landscape in human hepatocellular carcinoma","volume":"69","author":"Tsang","year":"2019","journal-title":"Hepatology"},{"issue":"20","key":"10.1016\/j.ejmech.2025.118489_bib19","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1158\/0008-5472.CAN-17-0314","article-title":"Therapeutic targeting of the CBP\/p300 bromodomain blocks the growth of castration-resistant prostate cancer","volume":"77","author":"Jin","year":"2017","journal-title":"Cancer Res."},{"issue":"26","key":"10.1016\/j.ejmech.2025.118489_bib20","doi-asserted-by":"crossref","first-page":"9308","DOI":"10.1021\/ja412434f","article-title":"Discovery and optimization of small-molecule ligands for the CBP\/p300 bromodomains","volume":"136","author":"Hay","year":"2014","journal-title":"J. Am. Chem. Soc."},{"issue":"22","key":"10.1016\/j.ejmech.2025.118489_bib21","doi-asserted-by":"crossref","first-page":"9162","DOI":"10.1021\/acs.jmedchem.7b00796","article-title":"GNE-781, A highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein, binding protein (CBP)","volume":"60","author":"Romero","year":"2017","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118489_bib22","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11523-023-00949-7","article-title":"FT-6876, a potent and selective inhibitor of CBP\/p300, is active in preclinical models of androgen receptor-positive breast cancer","volume":"18","author":"Caligiuri","year":"2023","journal-title":"Targeted Oncol."},{"issue":"1","key":"10.1016\/j.ejmech.2025.118489_bib23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/acs.jmedchem.1c01864","article-title":"Design, synthesis, and biological evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP bromodomain inhibitors for the treatment of prostate cancer","volume":"65","author":"Xiang","year":"2022","journal-title":"J. Med. Chem."},{"issue":"23","key":"10.1016\/j.ejmech.2025.118489_bib24","doi-asserted-by":"crossref","first-page":"10549","DOI":"10.1021\/acs.jmedchem.6b01022","article-title":"Discovery of a potent and selective in vivo probe (GNE-272) for the bromodomains of CBP\/EP300","volume":"59","author":"Crawford","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118489_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2022.116784","article-title":"Discovery of novel benzimidazole derivatives as potent p300 bromodomain inhibitors with anti-proliferative activity in multiple cancer cells","volume":"66","author":"Chen","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118489_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.105803","article-title":"Design, synthesis and biological evaluation of (R)-5-methylpyrrolidin-2-ones as p300 bromodomain inhibitors with anti-tumor activities in multiple tumor lines","volume":"124","author":"Liu","year":"2022","journal-title":"Bioorg. Chem."},{"issue":"20","key":"10.1016\/j.ejmech.2025.118489_bib27","doi-asserted-by":"crossref","first-page":"18606","DOI":"10.1021\/acs.jmedchem.4c01984","article-title":"Discovery of CZL-046 with an (S)-3-Fluoropyrrolidin-2-one scaffold as a p300 bromodomain inhibitor for the treatment of multiple myeloma","volume":"67","author":"Chen","year":"2024","journal-title":"J. Med. Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2025.118489_bib28","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1021\/acs.jmedchem.3c01905","article-title":"Discovery of a highly potent oxysterol receptor GPR183 antagonist bearing the benzo[d]thiazole structural motif for the treatment of inflammatory bowel disease (IBD)","volume":"67","author":"Zeng","year":"2024","journal-title":"J. Med. Chem."},{"issue":"17","key":"10.1016\/j.ejmech.2025.118489_bib29","doi-asserted-by":"crossref","first-page":"15711","DOI":"10.1021\/acs.jmedchem.4c01341","article-title":"Discovery of potent, specific, and orally available NLRP3 inflammasome inhibitors based on pyridazine scaffolds for the treatment of septic shock and peritonitis","volume":"67","author":"Fu","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118489_bib30","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jmedchem.4c01221","article-title":"Structure-guided conformational restriction leading to high-affinity, selective, and cell-active tetrahydroisoquinoline-based noncovalent Keap1-Nrf2 inhibitors","author":"Qin","year":"2024","journal-title":"J. Med. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2025.118489_bib31","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1016\/j.ccell.2023.11.001","article-title":"Therapeutic targeting of EP300\/CBP by bromodomain inhibition in hematologic malignancies","volume":"41","author":"Nicosia","year":"2023","journal-title":"Cancer Cell"},{"issue":"17","key":"10.1016\/j.ejmech.2025.118489_bib32","doi-asserted-by":"crossref","first-page":"11788","DOI":"10.1021\/acs.jmedchem.2c00909","article-title":"Tunable cysteine-targeting Electrophilic heteroaromatic warheads induce ferroptosis","volume":"65","author":"Karaj","year":"2022","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2025.118489_bib33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1039\/C8MD00327K","article-title":"Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors","volume":"10","author":"Keeley","year":"2019","journal-title":"MedChemComm"},{"issue":"12","key":"10.1016\/j.ejmech.2025.118489_bib34","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.201800184","article-title":"Heterocyclic electrophiles as new MurA inhibitors","volume":"351","author":"Keeley","year":"2018","journal-title":"Arch. Pharmazie"},{"issue":"9","key":"10.1016\/j.ejmech.2025.118489_bib35","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.1021\/acs.jmedchem.0c02232","article-title":"Development of dimethylisoxazole-attached Imidazo[1,2-a]pyridines as potent and selective CBP\/P300 inhibitors","volume":"64","author":"Muthengi","year":"2021","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.118489_bib36","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/0016-5085(89)90897-4","article-title":"Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability","volume":"96","author":"Hidalgo","year":"1989","journal-title":"Gastroenterology"},{"issue":"6","key":"10.1016\/j.ejmech.2025.118489_bib37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrd1108","article-title":"The impact of drug-induced QT interval prolongation on drug discovery and development","volume":"2","author":"Fermini","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"issue":"9","key":"10.1016\/j.ejmech.2025.118489_bib38","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.1021\/acs.jmedchem.3c02195","article-title":"Discovery of highly potent and efficient CBP\/p300 degraders with strong in vivo antitumor activity","volume":"67","author":"Hu","year":"2024","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012541?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012541?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:18:43Z","timestamp":1773929923000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425012541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":38,"alternative-id":["S0223523425012541"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118489","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of CZL-077 as a potent, selective, and orally active p300\/CBP bromodomain inhibitor with improved in vivo antitumor efficacy","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118489","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118489"}}