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These compounds were screened for antiproliferative effects across 60 human cancer cell lines. Compound\n                    <jats:bold>3f<\/jats:bold>\n                    was the most effective. Further evaluation at five concentrations to determine its GI\n                    <jats:sub>50<\/jats:sub>\n                    , TGI, and LC\n                    <jats:sub>50<\/jats:sub>\n                    . In vitro studies were conducted to evaluate its impact on EGFR signaling, cell cycle progression, apoptosis induction, and caspase\u20103 activation in T\u201047D cells. Compound\n                    <jats:bold>3f<\/jats:bold>\n                    showed greater selectivity toward cancerous T\u201047D cells over normal breast cells (MCF10a). Notably, compound\n                    <jats:bold>3f<\/jats:bold>\n                    displayed potent EGFR inhibition at submicromolar levels, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.121\u2009\u00b1\u20090.004\u2009\u03bcM, which was comparable to the reference inhibitor, erlotinib. Further investigations revealed that compound\n                    <jats:bold>3f<\/jats:bold>\n                    caused cell cycle arrest at the G2\/M phase in T\u201047D cells. Apoptosis analysis confirmed that compound\n                    <jats:bold>3f<\/jats:bold>\n                    induced cell death through programmed cell death, with a nearly 19\u2010fold increase in total apoptosis. This apoptotic mechanism was validated by a substantial rise in active caspase\u20103 levels. Molecular docking studies showed favorable binding of compound\n                    <jats:bold>3f<\/jats:bold>\n                    within the EGFR active site. Molecular dynamics simulations further confirmed the stability of compound\n                    <jats:bold>3f<\/jats:bold>\n                    within the active site over a 100\u2010ns simulation period, supporting its sustained interaction with key residues. Based on predictions of toxicity, compound\n                    <jats:bold>3f<\/jats:bold>\n                    was predicted to possess a favorable safety profile across 30 potential toxicities. Encouraged by its strong anticancer efficacy and safety profile, compound\n                    <jats:bold>3f<\/jats:bold>\n                    represents a compelling lead candidate for further development as a targeted treatment for breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70146","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:02:18Z","timestamp":1763787738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, Synthesis, Biological Evaluation, and In Silico Studies of Novel Furo[2,3\u2010\n                    <i>d<\/i>\n                    ]pyrimidine Derivatives as EGFR Inhibitors With Potential Antitumor Activity"],"prefix":"10.1002","volume":"358","author":[{"given":"Samar I.","family":"Faggal","sequence":"first","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Cairo University Cairo 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