{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:31:58Z","timestamp":1789687918293,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A new series of pyrazole\u2013thiazole\u2013oxadiazole hybrid compounds targeting the EGFR and VEGFR2 enzymes was designed and synthesized using innovative approaches. The compounds were characterized through spectral methods, and their cytotoxic activities were evaluated against the A549 lung and HT\u201029 colon cancer cell line using the MTT assay. Among them, compounds\n                    <jats:bold>17i<\/jats:bold>\n                    and\n                    <jats:bold>17m<\/jats:bold>\n                    exhibited notable cytotoxicity, with\n                    <jats:bold>17i<\/jats:bold>\n                    demonstrating approximately threefold greater activity compared to the reference drug sorafenib for A549 cells. Flow cytometry analysis revealed that\n                    <jats:bold>17i<\/jats:bold>\n                    induced extensive necrotic cell death, while\n                    <jats:bold>17m<\/jats:bold>\n                    triggered a more targeted and controlled apoptotic mechanism. In vitro enzyme inhibition assays demonstrated that\n                    <jats:bold>17i<\/jats:bold>\n                    inhibited EGFR and VEGFR2 with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.158 and 0.128\u2009\u00b5M, respectively. In contrast,\n                    <jats:bold>17m<\/jats:bold>\n                    exhibited more potent inhibition of EGFR (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.012\u2009\u00b5M) and moderate activity against VEGFR2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.309\u2009\u00b5M). Molecular docking and molecular dynamics simulations further supported the structural stability of the complexes formed by these compounds with their target enzymes, highlighting their potential as effective enzyme inhibitors. Collectively, these findings suggest that pyrazole\u2013thiazole\u2013oxadiazole hybrids represent promising candidates for targeted cancer therapy at the cellular level.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70122","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:52:56Z","timestamp":1760406776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Innovative Pyrazole\u2013Thiazole\u2013Oxadiazole Hybrid Compounds for Targeted EGFR\/VEGFR2 Inhibition in Cancer Treatment"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-7177","authenticated-orcid":false,"given":"Burak","family":"Kuzu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Van Yuzuncu Yil University Van 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