{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:46:34Z","timestamp":1790635594958,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Triple Negative Breast Cancer (TNBC) is one of the most aggressive subtypes of breast cancer (BC), which is associated with a very poor prognosis. It is a broad category of tumors with a variety of biological, clinical, and morphological characteristics. FOXM1 is a pivotal transcription factor that modulates proliferation\u2010associated genes through complex protein\u2010DNA and protein\u2010protein interactions, making it a highly attractive target in cancer therapy. However, existing small\u2010molecule inhibitors often suffer from limited specificity and efficacy. In this study, we designed, synthesized, and evaluated novel series of 2\u2010aminothiazole derivatives (\n                    <jats:bold>C1\u2010C15)<\/jats:bold>\n                    as potential FOXM1 inhibitors. Molecular docking and molecular dynamics (MD) simulations were employed to investigate the binding interactions of these compounds with the FOXM1 DNA\u2010binding domain (FOXM1\u2010DBD). Structural analysis highlighted the importance of crucial residues, including Asn283, His287, and Arg286, in mediating inhibitory activity. Among the synthesized compounds,\n                    <jats:bold>C11<\/jats:bold>\n                    exhibited remarkable structural alignment and interaction patterns with FOXM1\u2010DBD, comparable to the reference inhibitor FDI\u20106. In vitro studies using TNBC cell lines (MDA\u2010MB\u2010231, BT\u2010549, and BT\u201020) demonstrated that compound\n                    <jats:bold>C11<\/jats:bold>\n                    significantly outperformed FDI\u20106 in potency. Western blot analysis revealed that\n                    <jats:bold>C11<\/jats:bold>\n                    effectively suppressed FOXM1 transcriptional activity at concentrations of 10\u2009\u00b5M in BT\u2010549 cells and 20\u2009\u00b5M in MDA\u2010MB\u2010231 cells. These findings underscore the potential of\n                    <jats:bold>C11<\/jats:bold>\n                    as a potent FOXM1 inhibitor and highlight its promise for further development in TNBC therapy.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70296","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T20:59:42Z","timestamp":1777841982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Novel 2\u2010Aminothiazole Derivatives as Potential FOXM1 Inhibitors for Triple\u2010Negative Breast Cancer Therapy and Structure\u2010Activity Relationship"],"prefix":"10.1002","volume":"87","author":[{"given":"Khaled A. N.","family":"Abusharkh","sequence":"first","affiliation":[{"name":"Department of Chemistry, School of Graduate Studies \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"},{"name":"Department of Chemistry, Natural Products and Drug Research Laboratory, Faculty of Science \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"},{"name":"Department of Chemistry and Chemical Technology, Faculty of Science and Technology Al\u2010Quds University Jerusalem Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venhar","family":"\u00c7\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Erciyes University Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-0053","authenticated-orcid":false,"given":"Alper","family":"Onder","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Natural Products and Drug Research Laboratory, Faculty of Science \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2552-038X","authenticated-orcid":false,"given":"Merve","family":"S\u0131k\u0131k","sequence":"additional","affiliation":[{"name":"Department of Medical System Biology, School of Graduate Studies \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Mustafa Guzel","sequence":"additional","affiliation":[{"name":"Research Institute for Health Sciences and Technologies (SABITA), Center of Drug Discovery and Development Istanbul Medipol University \u0130stanbul T\u00fcrkiye"},{"name":"Department of Medical Pharmacology, International School of Medicine Istanbul Medipol University, Kavacik Campus, Kavacik\u2010Beykoz \u0130stanbul T\u00fcrkiye"},{"name":"Department of Basic Pharmaceutical Sciences, School of Pharmacy \u0130stanbul Medipol University Beykoz\u2010\u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhal","family":"Hamurcu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Erciyes University Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-9255","authenticated-orcid":false,"given":"Bulent","family":"Ozpolat","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine Houston Methodist Research Institute Houston Texas USA"},{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Ay","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Natural Products and Drug Research Laboratory, Faculty of Science \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-1979","authenticated-orcid":false,"given":"Ferah","family":"Comert Onder","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine \u00c7anakkale Onsekiz Mart University \u00c7anakkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4137\/BMI.S5740"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400504"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-024-02427-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/hc-2022-0008"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-020-02686-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43094-024-00759-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1959"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006593"},{"key":"e_1_2_10_10_1","unstructured":"Borzilleri R. M. R. S.Bhide J. S.Tokarski et al.2004. Heterocyclic Inhibitors of Kinases. 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