{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:16:11Z","timestamp":1785244571037,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      New series of thiazole analogues were designed, synthesized, and tested for their potential anticancer activity. All the synthesized compounds were biologically tested against HCT\u2010116 and MCF\u20107 cell lines. Compounds\n                      <jats:bold>14d<\/jats:bold>\n                      ,\n                      <jats:bold>14h<\/jats:bold>\n                      , and\n                      <jats:bold>14i<\/jats:bold>\n                      were determined to be the most active members in this series against HCT\u2010116 cancer cell lines with a considerable safety profile. The three lead compounds were further investigated for their inhibitory activities against EGFR and CDK\u20102. Compound\n                      <jats:bold>14i<\/jats:bold>\n                      exhibited the most potent inhibition, with IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 0.056 and 0.215\u2009\u00b5M against EGFR and CDK\u20102, respectively, suggesting a possible association between kinase inhibition and the observed cellular activity. Compounds\n                      <jats:bold>14d<\/jats:bold>\n                      ,\n                      <jats:bold>14h<\/jats:bold>\n                      , and\n                      <jats:bold>14i<\/jats:bold>\n                      induced early apoptosis (14.40%\u201318.09%) and G\n                      <jats:sub>2<\/jats:sub>\n                      \/M arrest (51.55%\u201366.15% population) in HCT\u2010116 cells, with minimal necrosis. Additionally, the screened compounds upregulated pro\u2010apoptotic factors (Bax, cytochrome c, and cleaved caspase\u20103), while downregulating pro\u2010survival\/anti\u2010apoptotic markers (p\u2010AKT1, Bcl\u20102) and the angiogenic factor VEGF, offering preliminary insight into the potential mechanism of action. EGFR and CDK\u20102 were among the most prominent genes identified in the network pharmacology analysis of the tested compounds. Molecular docking and molecular dynamics simulations suggested favorable binding modes of compound\n                      <jats:bold>14i<\/jats:bold>\n                      within the active sites of EGFR and CDK\u20102, with stable interaction patterns observed during the simulation period. Furthermore, compounds\n                      <jats:bold>14d<\/jats:bold>\n                      ,\n                      <jats:bold>14h<\/jats:bold>\n                      , and\n                      <jats:bold>14i<\/jats:bold>\n                      showed encouraging in silico ADMET and drug\u2010likeness profiles. Overall, these findings highlight the thiazole series as promising lead compounds with potential dual inhibitory activity, warranting further optimization and mechanistic validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ardp.70308","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:08:52Z","timestamp":1784286532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thiazole\u2010Derived Dual EGFR\/CDK\u20102 Inhibitors: Rational Design, Synthesis, In Vitro Anticancer Evaluation, Mechanistic Profiling, and Computational Binding Analysis"],"prefix":"10.1002","volume":"359","author":[{"given":"Rowida","family":"Nasr","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy, Mansoura University  Mansoura 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