{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:14:18Z","timestamp":1783570458944,"version":"3.55.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100012172","name":"Double First Class University Plan","doi-asserted-by":"publisher","award":["CPU2022PZQ16"],"award-info":[{"award-number":["CPU2022PZQ16"]}],"id":[{"id":"10.13039\/501100012172","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002857","name":"China Pharmaceutical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473792"],"award-info":[{"award-number":["82473792"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,4]]},"DOI":"10.1016\/j.bmc.2025.118082","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T12:18:28Z","timestamp":1737980308000},"page":"118082","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Discovery of novel spirocyclic derivates as potent androgen receptor antagonists"],"prefix":"10.1016","volume":"120","author":[{"given":"Wenqiang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuolin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2025.118082_b0005","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.bmc.2025.118082_b0010","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13215417","article-title":"Androgen receptor signaling in prostate cancer and therapeutic strategies","volume":"13","author":"Jacob","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.bmc.2025.118082_b0015","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/1477-3163.83937","article-title":"Androgen receptor signaling in prostate cancer development and progression","volume":"10","author":"Lonergan","year":"2011","journal-title":"J. Carcinog."},{"key":"10.1016\/j.bmc.2025.118082_b0020","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nrd.2016.120","article-title":"Drug discovery in advanced prostate cancer: translating biology into therapy","volume":"15","author":"Yap","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bmc.2025.118082_b0025","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/jcb.20811","article-title":"Androgen receptor action in hormone\u2010dependent and recurrent prostate cancer","volume":"99","author":"Agoulnik","year":"2006","journal-title":"J Cell Biochem"},{"key":"10.1016\/j.bmc.2025.118082_b0030","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2165\/00002512-199405010-00006","article-title":"Cyproterone - a review of its pharmacology and therapeutic efficacy in prostate-cancer","volume":"5","author":"Barradell","year":"1994","journal-title":"Drugs Aging"},{"key":"10.1016\/j.bmc.2025.118082_b0035","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/(SICI)1097-0045(19980101)34:1<61::AID-PROS8>3.0.CO;2-N","article-title":"Bicalutamide (Casodex\u00ae) in the treatment of prostate cancer: History of clinical development","volume":"34","author":"Kolvenbag","year":"1998","journal-title":"Prostate"},{"key":"10.1016\/j.bmc.2025.118082_b0040","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/S0140-6736(10)60172-9","article-title":"Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study","volume":"375","author":"Scher","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.bmc.2025.118082_b0045","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1002\/ijc.32242","article-title":"Darolutamide is a potent androgen receptor antagonist with strong efficacy in prostate cancer models","volume":"145","author":"Sugawara","year":"2019","journal-title":"Int J Cancer"},{"key":"10.1016\/j.bmc.2025.118082_b0050","doi-asserted-by":"crossref","first-page":"8253","DOI":"10.1200\/JCO.2005.03.4777","article-title":"Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis","volume":"23","author":"Scher","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.bmc.2025.118082_b0055","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.bmc.2025.118082_b0060","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1158\/1078-0432.CCR-10-0255","article-title":"Overcoming persistent dependency on androgen signaling after progression to castration-resistant prostate cancer","volume":"16","author":"Yamaoka","year":"2010","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0065","first-page":"3550","article-title":"Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer","volume":"61","author":"Linja","year":"2001","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0070","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nature11125","article-title":"The mutational landscape of lethal castration-resistant prostate cancer","volume":"487","author":"Grasso","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bmc.2025.118082_b0075","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2016.0494","article-title":"Genomic alterations in cell-free DNA and enzalutamide resistance in castration-resistant prostate cancer","volume":"2","author":"Wyatt","year":"2016","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.bmc.2025.118082_b0080","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.1073\/pnas.0500381102","article-title":"Structural basis for antagonism and resistance of bicalutamide in prostate cancer","volume":"102","author":"Bohl","year":"2005","journal-title":"PNAS"},{"key":"10.1016\/j.bmc.2025.118082_b0085","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N Engl J Med"},{"key":"10.1016\/j.bmc.2025.118082_b0090","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1172\/JCI41824","article-title":"Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant","volume":"120","author":"Sun","year":"2010","journal-title":"J Clin Invest"},{"key":"10.1016\/j.bmc.2025.118082_b0095","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0019059","article-title":"Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival","volume":"6","author":"Hornberg","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.bmc.2025.118082_b0100","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1158\/0008-5472.CAN-08-3795","article-title":"A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth","volume":"69","author":"Guo","year":"2009","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0105","first-page":"149","article-title":"Novel mutations of androgen receptor: A possible mechanism of bicalutamide withdrawal syndrome","volume":"63","author":"Hara","year":"2003","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0110","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.bmc.2025.118082_b0115","doi-asserted-by":"crossref","first-page":"13280","DOI":"10.1021\/acs.jmedchem.3c01264","article-title":"Discovery of ARD-1676 as a highly potent and orally efficacious AR PROTAC degrader with a broad activity against AR mutants for the treatment of AR + human prostate cancer","volume":"66","author":"Xiang","year":"2023","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0120","doi-asserted-by":"crossref","first-page":"8772","DOI":"10.1021\/acs.jmedchem.2c00716","article-title":"Therapeutic strategies to target the androgen receptor","volume":"65","author":"Xiang","year":"2022","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0125","doi-asserted-by":"crossref","first-page":"13487","DOI":"10.1021\/acs.jmedchem.1c00900","article-title":"Discovery of ARD-2585 as an exceptionally potent and orally active PROTAC degrader of androgen receptor for the treatment of advanced prostate cancer","volume":"64","author":"Xiang","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0130","doi-asserted-by":"crossref","first-page":"12642","DOI":"10.1021\/acs.jmedchem.0c00943","article-title":"Pyrazol-1-yl-propanamides as SARD and pan-antagonists for the treatment of enzalutamide-resistant prostate cancer","volume":"63","author":"He","year":"2020","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0135","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1021\/acs.jmedchem.8b00973","article-title":"New generation of selective androgen receptor degraders: our initial design, synthesis, and biological evaluation of new compounds with enzalutamide-resistant prostate cancer activity","volume":"62","author":"Hwang","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0140","doi-asserted-by":"crossref","first-page":"6764","DOI":"10.1158\/1078-0432.CCR-19-1458","article-title":"Orally bioavailable androgen receptor degrader, potential next-generation therapeutic for enzalutamide-resistant prostate cancer","volume":"25","author":"Ponnusamy","year":"2019","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0145","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1158\/0008-5472.CAN-17-0976","article-title":"Novel selective agents for the degradation of androgen receptor variants to treat castration-resistant prostate cancer","volume":"77","author":"Ponnusamy","year":"2017","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmc.2025.118082_b0150","doi-asserted-by":"crossref","first-page":"9659","DOI":"10.1002\/anie.201503720","article-title":"Small-molecule-mediated degradation of the androgen receptor through hydrophobic tagging","volume":"54","author":"Gustafson","year":"2015","journal-title":"Angew Chem Int Ed Engl"},{"key":"10.1016\/j.bmc.2025.118082_b0155","doi-asserted-by":"crossref","unstructured":"Petrylak DP, Stewart TF, Gao X, et al. A phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC). 2023;41:TPS290.","DOI":"10.1200\/JCO.2023.41.6_suppl.TPS290"},{"key":"10.1016\/j.bmc.2025.118082_b0160","doi-asserted-by":"crossref","unstructured":"Yu EY, Yazji S, Katz Y, et al. A phase 1\/2 study of ONCT-534, a dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer 2024;42:TPS241.","DOI":"10.1200\/JCO.2024.42.4_suppl.TPS241"},{"key":"10.1016\/j.bmc.2025.118082_b0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107433","article-title":"Discovery of novel biphenyl derivatives as androgen receptor degraders for the treatment of enzalutamide-resistant prostate cancer","volume":"148","author":"Zhang","year":"2024","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0170","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.eururo.2017.08.012","article-title":"Moving towards precision urologic oncology: targeting enzalutamide-resistant prostate cancer and mutated forms of the androgen receptor using the novel inhibitor darolutamide (ODM-201)","volume":"73","author":"Borgmann","year":"2018","journal-title":"Eur Urol"},{"key":"10.1016\/j.bmc.2025.118082_b0175","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2174\/0929867003375371","article-title":"Androgen receptor antagonists (antiandrogens) structure-activity relationships","volume":"7","author":"Singh","year":"2000","journal-title":"Curr Med Chem"},{"key":"10.1016\/j.bmc.2025.118082_b0180","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/cbdd.13848","article-title":"Analysis of the binding modes of the first- and second-generation antiandrogens with respect to F876L mutation","volume":"98","author":"Shao","year":"2021","journal-title":"Chem Biol Drug Des"},{"key":"10.1016\/j.bmc.2025.118082_b0185","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.bmc.2025.118082_b0190","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1016\/j.apsb.2022.05.003","article-title":"A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer","volume":"12","author":"Li","year":"2022","journal-title":"Acta Pharm Sin B"}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625000239?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089625000239?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T09:34:51Z","timestamp":1740476091000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089625000239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":38,"alternative-id":["S0968089625000239"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118082","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of novel spirocyclic derivates as potent androgen receptor antagonists","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2025.118082","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118082"}}