{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:27:54Z","timestamp":1787502474806,"version":"build-2736575974"},"reference-count":86,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"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":["The Chemical Record"],"abstract":"<jats:p>\n                    Pyrimidine has become an important scaffold for designing anticancer drugs because of its planar aromatic structure, synthetic versatility, and ability to establish key interactions with its target. This heterocyclic scaffold is an essential component of nucleic acids and many biologically active molecules, which makes it highly relevant for therapeutic application. In recent years, significant attention has been directed toward pyrimidine\u2010based hybrid molecules, in which the pyrimidine core is integrated with other bioactive scaffolds to enhance the anticancer activity. The present review encompasses a wide range of such hybrids, including pyrimidine\u2013quinoline, pyrimidine\u2013indole, pyrimidine\u2013triazole, pyrimidine\u2013chalcone, pyrimidine\u2013pyrazole, pyrimidine\u2013imidazole, pyrimidine\u2013thiazole, and pyrimidine\u2013oxadiazole derivatives. This hybridization strategy facilitates the development of multitargeted agents capable of modulating key signaling pathways in cancer. Among these, epidermal growth factor receptor (EGFR) has gained particular importance due to its central role in tumor growth, survival, and metastasis. This review focuses on the last 2 years\u2019 advancements (from Jan 2025 to early 2026) in the development of pyrimidine\u2010containing hybrid molecules as EGFR inhibitors. Different hybridization techniques involving pyrimidine linked or fused with another moiety are comprehensively discussed. Furthermore, the present review summarizes the structure\u2013activity relationship (SAR), mechanistic pathway, and molecular interactions responsible for their anticancer potential, with a specific emphasis on their EGFR inhibitory activity, including effects on mutant EGFR. Notably, compounds\n                    <jats:bold>16a<\/jats:bold>\n                    and\n                    <jats:bold>16b<\/jats:bold>\n                    (pyrazolo[3,4\u2010\n                    <jats:italic>d<\/jats:italic>\n                    ]pyrimidine\u2013sulfonamide hybrids) were identified as the most active EGFR inhibitors with IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.069 and 0.064\u2009\u00b5M, respectively. Additionally, pyrimidine\u2010based anticancer agents under clinical investigation as EGFR inhibitors are briefly highlighted. Overall, pyrimidine\u2010based hybrids represent a promising direction as next\u2010generation anticancer therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/tcr.70234","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:14:16Z","timestamp":1787501656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrimidine\u2010Based Hybrids for Epidermal Growth Factor Receptor Targeting: Structure\u2013Activity Relationships and Comparative Activity Profiling"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6212-9457","authenticated-orcid":false,"given":"Ankush","family":"Kumar","sequence":"first","affiliation":[{"name":"Chitkara College of Pharmacy Chitkara University  Rajpura Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-9562","authenticated-orcid":false,"given":"Rajwinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy Chitkara University  Rajpura Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-8749","authenticated-orcid":false,"given":"Rohit","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy Chitkara University  Rajpura Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel R. 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