{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:32:02Z","timestamp":1787567522605,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pyridopyrimidine is an important heterocyclic scaffold widely explored in anticancer drug discovery. Its structural similarity to purine enables effective interaction with various biological targets, mainly kinases involved in cancer progression. This manuscript presents recent developments reported between 2021 and 2026, focusing on the biological evaluation, and structure\u2013activity relationships of pyridopyrimidine derivatives. Many of these synthesized compounds act as inhibitors of key targets such as EGFR, CDK4\/6, and the PI3K\/mTOR pathway, which are closely associated with tumor growth, survival, and resistance mechanisms. Other targets such as ATR and PIM are also explored. Recent studies show that structural modifications, including substitution on the core ring and hybridization with pharmacologically active moieties like triazoles and thiazolidinediones, significantly improve anticancer activity. Several derivatives have demonstrated strong antiproliferative effects against different cancer cell lines and are capable of inducing apoptosis and cell cycle arrest. In addition, molecular docking and other computational studies support their binding efficiency and help explain their mechanisms of action. There is also increasing interest in the development of dual-target or multi-target inhibitors to overcome drug resistance and enhance therapeutic effectiveness. Overall, pyridopyrimidine- and pyridopyrimidinones-based compounds continue to show great promise as potential anticancer agents. Further research combining synthetic chemistry, biological studies, and computational approaches may lead to the development of more effective and safer drugs in the future.<\/jats:p>","DOI":"10.3390\/molecules31172944","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyridopyrimidines and Pyridopyrimidinones as Kinase-Targeted Anticancer Agents: Medicinal Chemistry and Mechanistic Insights"],"prefix":"10.3390","volume":"31","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 140401, 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 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-6294","authenticated-orcid":false,"given":"Bhupinder","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, HNB Garhwal University, Srinagar 246174, Uttarakhand, 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 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3892\/ijmm.2017.3036","article-title":"The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy","volume":"40","author":"Ardito","year":"2017","journal-title":"Int. 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