{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:27:45Z","timestamp":1790638065385,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LIGUE CONTRE LE CANCER - COMITE LANGUEDOC-ROUSSILLON","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Prostate cancer is the most commonly diagnosed malignancy in men. Its growth mainly relies on the activity of the androgen receptor (AR), justifying the use of androgen deprivation therapy as a gold standard treatment for the metastatic disease. Inhibition of the androgen axis using second generation antagonists has improved patients\u2019 survival, but is systematically confronted to resistance mechanisms, leading to a median survival that does not exceed 5 years. Counteracting this resistance has been the object of a large number of investigations, with a particular emphasis towards the identification of new AR inhibitors, whether they antagonize the receptor by a competitive or a non-competitive binding. To this end, many high content screens have been performed, to identify new non-steroidal AR antagonists, using a variety of approaches, but reported somewhat controversial results, depending on the approach and on the cell model that was used for screening. In our study, we used the U2OS osteosarcoma cells stably transfected with AR or ARv7 and a luciferase reporter as a previously validated model to screen the Prestwick Phytochemical library. The results of our screen identified ellipticine, harmol, and harmine hydrochloride as confirmed hits. Surprisingly, we could demonstrate that harmol hydrochloride, previously identified as a non-competitive inhibitor of AR or a weak inhibitor of androgen signaling, was actually a competitive antagonist of AR, which inhibits the growth of VCaP prostate cancer line, at concentrations for which it did not affect the growth of the AR negative DU145 and PC3 cells. Interestingly, we also report for the first time that harmol hydrochloride was selective for AR, as it could not alter the activity of other nuclear receptors, such as the glucocorticoid receptor (GR), the progesterone receptor (PR), or the mineralocorticoid receptor (MR). Additionally, we demonstrate that, conversely to enzalutamide, harmol hydrochloride did not show any agonistic activity towards the pregnane X receptor (PXR), a master regulator of drug metabolism. Together, our results shed light on the importance of the cellular context for the screening of new AR antagonists. They further indicate that some of the potential hits that were previously identified may have been overlooked.<\/jats:p>","DOI":"10.3390\/cells9061469","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T13:20:43Z","timestamp":1592313643000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor"],"prefix":"10.3390","volume":"9","author":[{"given":"Hadjer","family":"Dellal","sequence":"first","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhay","family":"Boulahtouf","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"},{"name":"Institut r\u00e9gional du Cancer de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Alaterre","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Cuenant","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-7719","authenticated-orcid":false,"given":"William","family":"Bourguet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"},{"name":"Centre de Biochimie Structurale, CNRS, INSERM, Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Gongora","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-3622","authenticated-orcid":false,"given":"Patrick","family":"Balaguer","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5326-3005","authenticated-orcid":false,"given":"Philippe","family":"Pourquier","sequence":"additional","affiliation":[{"name":"IRCM, Institut de Recherche en Canc\u00e9rologie de Montpellier, INSERM U1194, F-34298 Montpellier, France"},{"name":"Universit\u00e9 de Montpellier, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/jcp.25099","article-title":"Androgen Receptor Coactivators in Regulation of Growth and Differentiation in Prostate Cancer","volume":"231","author":"Culig","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_3","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":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fonc.2018.00180","article-title":"Mechanisms and Approaches for Overcoming Enzalutamide Resistance in Prostate Cancer","volume":"8","author":"Cao","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kita, Y., Goto, T., Akamatsu, S., Yamasaki, T., Inoue, T., Ogawa, O., and Kobayashi, T. (2018). Castration-Resistant Prostate Cancer Refractory to Second-Generation Androgen Receptor Axis-Targeted Agents: Opportunities and Challenges. Cancers, 10.","DOI":"10.3390\/cancers10100345"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s40610-017-0079-1","article-title":"Molecular Mechanisms of Enzalutamide Resistance in Prostate Cancer","volume":"3","author":"Culig","year":"2017","journal-title":"Curr. Mol. Biol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Crona, D.J., and Whang, Y.E. (2017). Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance. Cancers, 9.","DOI":"10.3390\/cancers9060067"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrurol.2016.212","article-title":"Prostate cancer: AR aberrations and resistance to abiraterone or enzalutamide","volume":"13","author":"Attard","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nm972","article-title":"Molecular determinants of resistance to antiandrogen therapy","volume":"10","author":"Chen","year":"2004","journal-title":"Nat. Med."},{"key":"ref_10","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":"ref_11","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":"ref_12","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1158\/0008-5472.CAN-08-0594","article-title":"Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance","volume":"68","author":"Dehm","year":"2008","journal-title":"Cancer Res."},{"key":"ref_13","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":"ref_14","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/ijc.10495","article-title":"Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancer","volume":"100","author":"Steketee","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_15","first-page":"365","article-title":"Mechanisms of resistance in castration-resistant prostate cancer (CRPC)","volume":"4","author":"Chandrasekar","year":"2015","journal-title":"Transl. Androl. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.bmcl.2016.12.022","article-title":"In silico selection and cell-based characterization of selective and bioactive compounds for androgen-dependent prostate cancer cell","volume":"27","author":"Cruz","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wahl, J., and Smie\u0161ko, M. (2018). Endocrine Disruption at the Androgen Receptor: Employing Molecular Dynamics and Docking for Improved Virtual Screening and Toxicity Prediction. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061784"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112156","DOI":"10.1016\/j.ejmech.2020.112156","article-title":"Novel androgen receptor antagonist identified by structure-based virtual screening, structural optimization, and biological evaluation","volume":"192","author":"Tang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1021\/ci300514v","article-title":"Identification of novel androgen receptor antagonists using structure- and ligand-based methods","volume":"53","author":"Li","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.drudis.2012.06.018","article-title":"Structure-based methods for predicting target mutation-induced drug resistance and rational drug design to overcome the problem","volume":"17","author":"Hao","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cbi.2017.07.023","article-title":"Iminoenamine based novel androgen receptor antagonist exhibited anti-prostate cancer activity in androgen independent prostate cancer cells through inhibition of AKT pathway","volume":"275","author":"Divakar","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1089\/adt.2016.716","article-title":"Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells","volume":"14","author":"Johnston","year":"2016","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/acsmedchemlett.6b00186","article-title":"Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer","volume":"7","author":"Johnson","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ccr.2006.09.005","article-title":"Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators","volume":"10","author":"Hieronymus","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7233","DOI":"10.1073\/pnas.0807282106","article-title":"Non-competitive androgen receptor inhibition in vitro and in vivo","volume":"106","author":"Jones","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1021\/cb800054w","article-title":"A cellular conformation-based screen for androgen receptor inhibitors","volume":"3","author":"Jones","year":"2008","journal-title":"ACS Chem. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/toxsci\/kfi005","article-title":"Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays","volume":"83","author":"Sonneveld","year":"2005","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tox.2019.04.003","article-title":"Functional profiling of bisphenols for nuclear receptors","volume":"420","author":"Grimaldi","year":"2019","journal-title":"Toxicology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1021\/tx7002382","article-title":"Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism","volume":"21","author":"Vinggaard","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.2174\/0929867325666180913095239","article-title":"Non-Steroidal Androgen Receptor Antagonists and Prostate Cancer: A Survey on Chemical Structures Binding this Fast-Mutating Target","volume":"26","author":"Ferroni","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fontana, F., Raimondi, M., Marzagalli, M., Di Domizio, A., and Limonta, P. (2020). Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets. Cells, 9.","DOI":"10.3390\/cells9020460"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0303-7207(99)00251-8","article-title":"A stable prostatic bioluminescent cell line to investigate androgen and antiandrogen effects","volume":"160","author":"Tahiri","year":"2000","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8089","DOI":"10.1038\/ncomms9089","article-title":"Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds","volume":"6","author":"Delfosse","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14930","DOI":"10.1073\/pnas.1203574109","article-title":"Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes","volume":"109","author":"Delfosse","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/EC-19-0340","article-title":"AR mRNA stability is increased with AR-antagonist resistance via 3\u2019UTR variants","volume":"9","author":"Dart","year":"2020","journal-title":"Endocr. Connect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1158\/1535-7163.MCT-12-0798","article-title":"A novel antiandrogen, Compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth in vitro and in vivo","volume":"12","author":"Kuruma","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1158\/0008-5472.CAN-13-0359","article-title":"Cotargeting Androgen Receptor and Clusterin Delays Castrate-Resistant Prostate Cancer Progression by Inhibiting Adaptive Stress Response and AR Stability","volume":"73","author":"Matsumoto","year":"2013","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41976","DOI":"10.18632\/oncotarget.5659","article-title":"Reciprocal feedback inhibition of the androgen receptor and PI3K as a novel therapy for castrate-sensitive and -resistant prostate cancer","volume":"6","author":"Qi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_39","first-page":"2689","article-title":"Combination of phospholipase C\u03b5 knockdown with GANT61 sensitizes castration-resistant prostate cancer cells to enzalutamide by suppressing the androgen receptor signaling pathway","volume":"41","author":"Sun","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1006\/abio.2001.5352","article-title":"Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor","volume":"298","author":"Blankvoort","year":"2001","journal-title":"Anal. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0039-128X(02)00112-5","article-title":"Receptor profiling and endocrine interactions of tibolone","volume":"68","author":"Deckers","year":"2003","journal-title":"Steroids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0303-7207(02)00094-1","article-title":"Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines","volume":"193","author":"Paris","year":"2002","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/toxsci\/66.1.69","article-title":"A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists","volume":"66","author":"Wilson","year":"2002","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.14440\/jbm.2015.63","article-title":"In vitro and in vivo model systems used in prostate cancer research","volume":"2","author":"Cunningham","year":"2015","journal-title":"J. Biol. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/0960-0760(92)90086-X","article-title":"Stable transfection of androgen receptor and MMTV-CAT into mammalian cells: Inhibition of cat expression by anti-androgens","volume":"42","author":"Fuhrmann","year":"1992","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.tiv.2006.03.003","article-title":"Comparison of prostate cancer cell lines for androgen receptor-mediated reporter gene assays","volume":"20","author":"Kim","year":"2006","journal-title":"Toxicol. In Vitro"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/toxsci\/66.1.82","article-title":"Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and\/or hAR for endocrine screening","volume":"66","author":"Hartig","year":"2002","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2174\/09298673113206660272","article-title":"Ellipticines as DNA-targeted chemotherapeutics","volume":"21","author":"Frei","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.cmet.2007.03.010","article-title":"The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARgamma expression","volume":"5","author":"Waki","year":"2007","journal-title":"Cell Metab."},{"key":"ref_50","first-page":"1","article-title":"Discovery of beta-carboline ligands for benzodiazepine receptors","volume":"11","author":"Braestrup","year":"1993","journal-title":"Psychopharmacol. Ser."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1021\/cr0304469","article-title":"Comparative quantitative structure-activity relationship studies (QSAR) on non-benzodiazepine compounds binding to benzodiazepine receptor (BzR)","volume":"104","author":"Garg","year":"2004","journal-title":"Chem. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/002215540405200103","article-title":"Immunohistochemical assessment of the peripheral benzodiazepine receptor in human tissues","volume":"52","author":"Bribes","year":"2004","journal-title":"J. Histochem. Cytochem. Off. J. Histochem. Soc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1517\/17425255.2016.1141196","article-title":"Nuclear receptors and drug metabolism for the personalization of cancer therapy","volume":"12","author":"Cecchin","year":"2016","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_54","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\u20132 study","volume":"375","author":"Scher","year":"2010","journal-title":"Lancet Lond. Engl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s40262-015-0271-5","article-title":"Clinical Pharmacokinetic Studies of Enzalutamide","volume":"54","author":"Gibbons","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s40262-016-0403-6","article-title":"Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide","volume":"55","author":"Benoist","year":"2016","journal-title":"Clin. Pharmacokinet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/dta.1344","article-title":"Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca","volume":"4","author":"Riba","year":"2012","journal-title":"Drug Test. Anal."},{"key":"ref_58","first-page":"359","article-title":"Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism","volume":"9","author":"Shiau","year":"2002","journal-title":"Nat. Struct. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1469\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:39:23Z","timestamp":1760175563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,16]]},"references-count":58,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cells9061469"],"URL":"https:\/\/doi.org\/10.3390\/cells9061469","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,16]]}}}