{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:36:09Z","timestamp":1778679369890,"version":"3.51.4"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100008092","name":"Jinhua City Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008092","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":[[2026,8]]},"DOI":"10.1016\/j.ejmech.2026.118862","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:07:13Z","timestamp":1776701233000},"page":"118862","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["A novel small-molecule androgen receptor antagonist selective for the T878A-mutant AR in prostate cancer therapy"],"prefix":"10.1016","volume":"312","author":[{"given":"Yangyang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huating","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luhu","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganpeng","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qunce","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenteng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingjun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-5952","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118862_bib1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.ejmech.2026.118862_bib2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJMra1701695","article-title":"Metastatic prostate cancer","volume":"378","author":"Sartor","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2026.118862_bib4","first-page":"3","article-title":"Androgen receptor structure, function and biology: from bench to bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"10.1016\/j.ejmech.2026.118862_bib5","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.3390\/cells9122653","article-title":"Androgen receptor signaling pathway in prostate cancer: from genetics to clinical applications","volume":"9","author":"Aurilio","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.ejmech.2026.118862_bib6","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a030635","article-title":"Treatment of advanced prostate Cancer-A review of current therapies and future promise","volume":"8","author":"Sumanasuriya","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib7","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/j.1742-1241.2011.02799.x","article-title":"Characterising the castration-resistant prostate cancer population: a systematic review","volume":"65","author":"Kirby","year":"2011","journal-title":"Int. J. Clin. Pract."},{"key":"10.1016\/j.ejmech.2026.118862_bib8","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.semcancer.2021.09.007","article-title":"Microbiota and prostate cancer","volume":"86","author":"Rizzo","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.ejmech.2026.118862_bib9","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.ctrv.2015.08.002","article-title":"Understanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer","volume":"41","author":"Buttigliero","year":"2015","journal-title":"Cancer Treat Rev."},{"key":"10.1016\/j.ejmech.2026.118862_bib10","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a030452","article-title":"Androgen signaling in prostate cancer","volume":"7","author":"Dai","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib11","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1530\/ERC-22-0140","article-title":"Androgen receptor mutations for precision medicine in prostate cancer","volume":"29","author":"Shiota","year":"2022","journal-title":"Endocr. Relat. Cancer"},{"key":"10.1016\/j.ejmech.2026.118862_bib12","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1210\/endrev\/bnab002","article-title":"Hormonal therapy for prostate cancer","volume":"42","author":"Desai","year":"2021","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.ejmech.2026.118862_bib13","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13059-015-0864-1","article-title":"Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients","volume":"17","author":"Lallous","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.ejmech.2026.118862_bib14","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1001\/jamaoncol.2024.0591","article-title":"Metastatic hormone-sensitive prostate cancer and combination treatment outcomes: a review","volume":"10","author":"Hussain","year":"2024","journal-title":"JAMA Oncol."},{"key":"10.1016\/j.ejmech.2026.118862_bib15","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"PREVAIL investigators, enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for metastatic, castration-sensitive prostate cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib17","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJMoa2119115","article-title":"ARASENS trial investigators, darolutamide and survival in metastatic, hormone-sensitive prostate cancer","volume":"386","author":"Smith","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41391-020-00296-y","article-title":"Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer","volume":"24","author":"Hussain","year":"2021","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"10.1016\/j.ejmech.2026.118862_bib19","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003180","article-title":"Beyond PSA: the next generation of prostate cancer biomarkers","volume":"4","author":"Prensner","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib20","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2165\/00002018-199717030-00002","article-title":"Pharmacological importance of stereochemical resolution of enantiomeric drugs","volume":"17","author":"Islam","year":"1997","journal-title":"Drug Saf."},{"key":"10.1016\/j.ejmech.2026.118862_bib21","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2019.00801","article-title":"Second-generation antiandrogens: from discovery to standard of care in castration resistant prostate cancer","volume":"9","author":"Rice","year":"2019","journal-title":"Front. Oncol."},{"key":"10.1016\/j.ejmech.2026.118862_bib22","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.1168175","article-title":"Development of a second-generation antiandrogen for treatment of advanced prostate cancer","volume":"324","author":"Tran","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118862_bib23","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1158\/0008-5472.CAN-11-3948","article-title":"ARN-509: a novel antiandrogen for prostate cancer treatment","volume":"72","author":"Clegg","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2026.118862_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/srep12007","article-title":"Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies","volume":"5","author":"Moilanen","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2026.118862_bib25","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1126\/science.1117679","article-title":"Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer","volume":"310","author":"Tomlins","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118862_bib26","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.cell.2009.04.056","article-title":"Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer","volume":"138","author":"Wang","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2026.118862_bib27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/20014091084236","article-title":"The role of molecular forms of prostate-specific antigen (PSA or hK3) and of human glandular kallikrein 2 (hK2) in the diagnosis and monitoring of prostate cancer and in extra-prostatic disease","volume":"38","author":"Becker","year":"2001","journal-title":"Crit. Rev. Clin. Lab Sci."},{"key":"10.1016\/j.ejmech.2026.118862_bib28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.pharmthera.2013.01.011","article-title":"Targeting cell cycle regulation in cancer therapy","volume":"138","author":"Diaz-Moralli","year":"2013","journal-title":"Pharmacol. Therapeut."},{"key":"10.1016\/j.ejmech.2026.118862_bib29","doi-asserted-by":"crossref","first-page":"R141","DOI":"10.1530\/ERC-20-0517","article-title":"Novel insights in cell cycle dysregulation during prostate cancer progression","volume":"28","author":"Ben-Salem","year":"2021","journal-title":"Endocr. Relat. Cancer"},{"key":"10.1016\/j.ejmech.2026.118862_bib30","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1007\/s00018-002-8510-y","article-title":"Cyclin A in cell cycle control and cancer","volume":"59","author":"Yam","year":"2002","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.ejmech.2026.118862_bib31","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/med.21558","article-title":"A magic drug target: androgen receptor","volume":"39","author":"Li","year":"2019","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118862_bib32","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/S0006-291X(05)80067-1","article-title":"A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens","volume":"173","author":"Veldscholte","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2026.118862_bib33","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1158\/2159-8290.CD-13-0142","article-title":"An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (Enzalutamide)","volume":"3","author":"Korpal","year":"2013","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118862_bib34","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1158\/2159-8290.CD-13-0226","article-title":"A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509","volume":"3","author":"Joseph","year":"2013","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118862_bib35","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1056\/NEJM199505253322101","article-title":"Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer","volume":"332","author":"Taplin","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118862_bib36","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1021\/bi061321b","article-title":"The androgen receptor T877A mutant recruits LXXLL and FXXLF peptides differently than wild-type androgen receptor in a time-resolved fluorescence resonance energy transfer assay","volume":"46","author":"Ozers","year":"2007","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejmech.2026.118862_bib37","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1158\/1535-7163.MCT-15-0892","article-title":"The effect of F877L and T878A mutations on androgen receptor response to enzalutamide","volume":"15","author":"Prekovic","year":"2016","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2026.118862_bib38","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1158\/1078-0432.CCR-14-2666","article-title":"Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer","volume":"21","author":"Azad","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2026.118862_bib39","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1002\/pro.3496","article-title":"The nuclear receptor superfamily: a structural perspective","volume":"27","author":"Weikum","year":"2018","journal-title":"Protein Sci."},{"key":"10.1016\/j.ejmech.2026.118862_bib40","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.gpb.2018.03.007","article-title":"Discovery of novel androgen receptor ligands by structure-based virtual screening and bioassays","volume":"16","author":"Zhou","year":"2018","journal-title":"Genom. Proteom. Bioinform."},{"key":"10.1016\/j.ejmech.2026.118862_bib41","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1021\/acs.jmedchem.1c01938","article-title":"Discovery of N-(4-(Benzyloxy)-phenyl)-sulfonamide derivatives as novel antagonists of the human androgen receptor targeting the activation function 2","volume":"65","author":"Chai","year":"2022","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:S0223523426003077?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426003077?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:56:33Z","timestamp":1778676993000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426003077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":41,"alternative-id":["S0223523426003077"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118862","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A novel small-molecule androgen receptor antagonist selective for the T878A-mutant AR in prostate cancer therapy","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118862","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 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":"118862"}}