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In this study, four novel tamoxifen\u2010based dimers were synthesized and evaluated for their antitumor activities. Among these, (\n                    <jats:italic>Z,Z<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1<\/jats:bold>\n                    exhibited potent antiproliferative effects in ER+ cells, demonstrating selective toxicity toward cancer cells over normal cells. (\n                    <jats:italic>Z,Z<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1<\/jats:bold>\n                    significantly outperformed tamoxifen with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 9.18\u2009\u03bcM (24\u2009h) and 6.86\u2009\u03bcM (48\u2009h) against MCF\u20107 cells. Additionally, it showed greater selectivity toward ER+ breast cancer cells compared with both triple\u2010negative cancer cells and non\u2010cancerous cells. Mechanistic studies indicated that (\n                    <jats:italic>Z,Z<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1<\/jats:bold>\n                    induces apoptosis in MCF\u20107 cells through a cell\u2010cycle\u2010independent mechanism, unlike TMX, which arrests cells at the G0\/G1 phase. These findings suggest that (\n                    <jats:italic>Z,Z<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1<\/jats:bold>\n                    may be a promising candidate for further development as an alternative to tamoxifen therapy in ER+ breast cancer treatment. The docking studies revealed that (\n                    <jats:italic>Z,Z<\/jats:italic>\n                    )\u2010\n                    <jats:bold>1<\/jats:bold>\n                    exhibits the strong binding affinity to ER\u03b1, highlighting its potential as a promising therapeutic candidate for ER+ breast cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70260","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:11:38Z","timestamp":1779448298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tamoxifen\u2010Based Dimers: Design, Synthesis, Cell Viability Evaluation on Breast Cancer Cells, and Computational Insights"],"prefix":"10.1002","volume":"359","author":[{"given":"Berrak","family":"Ertugrul","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Ataturk University Erzurum T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmelik","family":"Aytatli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Erzurum Technical University Erzurum T\u00fcrkiye"},{"name":"Molecular Cancer Biology Laboratory, High Technology Application and Research Center Erzurum Technical University Erzurum T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer Faruk","family":"Karatas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Erzurum Technical University Erzurum T\u00fcrkiye"},{"name":"Molecular Cancer Biology Laboratory, High Technology Application and Research Center Erzurum Technical University Erzurum T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selcuk","family":"Essiz","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services Hakkari University Hakkari T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Aksakal","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy Kocaeli Health and Technology University Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-7480","authenticated-orcid":false,"given":"Nurullah","family":"Saracoglu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Ataturk University Erzurum T\u00fcrkiye"},{"name":"Biotechnology Institute Ankara University Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2021.0459"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.26444\/aaem\/75943"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20211033"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01208-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4331\/wjbc.v6.i3.231"},{"key":"e_1_2_8_8_1","article-title":"MIR497HG\u2010Derived miR\u2010195 and miR\u2010497 Mediate Tamoxifen Resistance via PI3K\/AKT Signaling in Breast Cancer","volume":"10","author":"Tian Y.","year":"2023","journal-title":"Advancement of Science"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109602"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-015-0514-2"},{"key":"e_1_2_8_11_1","first-page":"4007","article-title":"Effects of Tamoxifen on Cell Cycle Progression of Synchronous MCF\u20107 Human Mammary Carcinoma Cells","volume":"43","author":"Taylor I. 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