{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:12:53Z","timestamp":1786119173561,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A new series of pyrazolo[3,4\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]pyridine and spiro\u2010oxindole derivatives were rationally designed, synthesized, and biologically assessed as either CDK2 or EGFR inhibitors with potential anticancer activity. The CDK2 inhibitory evaluation of pyrazolo[3,4\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]pyridines\n                    <jats:bold>6a\u2013g<\/jats:bold>\n                    and\n                    <jats:bold>7a\u2013f<\/jats:bold>\n                    revealed that compounds\n                    <jats:bold>6e<\/jats:bold>\n                    ,\n                    <jats:bold>7b<\/jats:bold>\n                    , and\n                    <jats:bold>7c<\/jats:bold>\n                    exhibited potent inhibition (IC\u2085\u2080\u2009=\u20090.88, 1.89, and 1.23\u2009\u03bcM, respectively), compared to roscovitine (IC\u2085\u2080\u2009=\u20090.84\u2009\u03bcM). Among the spiro\u2010oxindole derivatives\n                    <jats:bold>8a\u2013d<\/jats:bold>\n                    , compounds\n                    <jats:bold>8b<\/jats:bold>\n                    and\n                    <jats:bold>8c<\/jats:bold>\n                    demonstrated remarkable EGFR inhibition (IC\u2085\u2080\u2009=\u20090.13 and 0.09\u2009\u03bcM, respectively) and significant activity against mutant EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    (IC\u2085\u2080\u2009=\u20090.32 and 0.14\u2009\u03bcM) relative to gefitinib (IC\u2085\u2080\u2009=\u20090.03 and 0.18\u2009\u03bcM, respectively). Furthermore, compounds\n                    <jats:bold>6e<\/jats:bold>\n                    and\n                    <jats:bold>8c<\/jats:bold>\n                    exhibited selective cytotoxicity versus MCF\u20107 and MDA\u2010MB231 cancer cells, respectively, with negligible cytotoxic effects on normal Vero cells. Flow cytometric analysis confirmed that compounds\n                    <jats:bold>6e<\/jats:bold>\n                    and\n                    <jats:bold>8c<\/jats:bold>\n                    induced G1\u2010phase cell cycle arrest and apoptosis in MCF\u20107 and MDA\u2010MB\u2010231, respectively, accompanied by a pronounced increase in the Bax\/Bcl\u20102 ratio, with values of 12.15 and 16.93 fold, respectively. Molecular docking studies combined with molecular dynamics simulations further supported stable ligand\u2013protein interactions within CDK2, EGFR, and mutant EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    active sites, with favorable binding energies and conformational stability throughout 100\u2009ns trajectories. Collectively, these findings identify compounds\n                    <jats:bold>6e<\/jats:bold>\n                    and\n                    <jats:bold>8c<\/jats:bold>\n                    as promising lead scaffolds for further development of CDK2 or EGFR inhibitors with potent and selective anticancer properties.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70263","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:28:36Z","timestamp":1773034116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Pyrazolo[3,4\u2010\n                    <i>b<\/i>\n                    ]Pyridine and Spiro\u2010Oxindole Hybrids as Selective CDK2 or EGFR Inhibitors for Targeted Cancer Therapy: Design, Synthesis, and Molecular Modeling Insights"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1868-7930","authenticated-orcid":false,"given":"Ahmed K. B. A. W.","family":"Farouk","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"},{"name":"School of Life and Medical Sciences University of Hertfordshire Hosted by Global Academic Foundation Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya A. A.","family":"Al\u2010Tanany","sequence":"additional","affiliation":[{"name":"Postgraduate Program of Pharmaceutical Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"},{"name":"Department of Central Administration of Pharmaceutical Policies and Market Access Egyptian Drug Authority Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0434-2369","authenticated-orcid":false,"given":"Mohamed R.","family":"Elnagar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Al\u2010Azhar University Cairo Egypt"},{"name":"Department of Pharmacology, College of Pharmacy The Islamic University Najaf Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-0562","authenticated-orcid":false,"given":"Mohamed M.","family":"Tawfik","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3888","authenticated-orcid":false,"given":"Mohamed K.","family":"El\u2010Ashrey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"},{"name":"Medicinal Chemistry Department, Faculty of Pharmacy King Salman International University South Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2413-9539","authenticated-orcid":false,"given":"Safinaz E.\u2010S.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-2504","authenticated-orcid":false,"given":"Hatem 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