{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:06:31Z","timestamp":1789563991183,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"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":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vascular endothelial growth factor receptor\u20102 (VEGFR\u20102) is a vital mediator of angiogenesis. Therefore, VEGFR\u20102 inhibition is considered a promising therapeutic target to combat cancer. In the present study, a series of 22 imidazo[4,5\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]pyridine\u2010acrylonitrile\u2010based derivatives was designed and synthesized. All compounds were evaluated for their VEGFR\u20102 inhibitory activity. Seven of the tested compounds showed high inhibitory activity against VEGFR\u20102 with IC\n                    <jats:sub>50<\/jats:sub>\n                    (0.029\u20130.087\u2009\u00b5M) compared to reference drug sorafenib IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.091\u2009\u00b5M. Four of these derivatives were selected for in vitro cytotoxic activity against breast cancer (MCF\u20107) and hepatocellular (HepG2) carcinoma cell lines, showing IC\n                    <jats:sub>50<\/jats:sub>\n                    (0.073\u20130.196\u2009\u00b5M) and (0.20\u20130.21\u2009\u00b5M), respectively, relative to sorafenib IC\n                    <jats:sub>50<\/jats:sub>\n                    0.16 and 0.19\u2009\u00b5M, respectively. Compound\n                    <jats:bold>2f<\/jats:bold>\n                    exhibiting a superior VEGFR\u20102 inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.029\u2009\u00b5M compared to sorafenib IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.091\u2009\u00b5M) and cytotoxicity against MCF\u20107 and HepG2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.073\u2009\u00b5M and IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.09\u2009\u00b5M, respectively), was subjected to cell cycle analysis, apoptosis assay, and molecular modeling studies, which strongly supported the results. It caused cell cycle arrest at G2\/M phase by 13.67% and a promising apoptosis induction.\n                    <jats:bold>2f<\/jats:bold>\n                    exhibited a promising binding score and pose inside the VEGFR\u20102 active sites. It also showed a good safety profile with a moderate selectivity index. Based on the prediction of physicochemical and pharmacokinetic properties for\n                    <jats:bold>2f<\/jats:bold>\n                    , it showed excellent prediction results to be orally bioavailable.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70385","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:01:13Z","timestamp":1789534873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, In Vitro Biological Evaluation, and In Silico Studies of Novel Imidazo[4,5\u2010\n                    <i>b<\/i>\n                    ]Pyridine\u2010Acrylonitrile\u2010Based Derivatives as VEGFR\u20102 Inhibitors Against Breast Cancer and Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6741-3983","authenticated-orcid":false,"given":"Lamia W.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Saadeldin","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy Cairo University Cairo Egypt"},{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Ahram Canadian University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-0491","authenticated-orcid":false,"given":"Ayman B.","family":"Farag","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Ahram Canadian University Giza Egypt"},{"name":"Department of Cardiology, Sarver Heart Center University of Arizona Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.04.068"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673402314251104071536"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106032"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA05244G"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz382"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004\u2010024\u201001179\u20102"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.24820\/ark.5550190.p011.415"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202004584"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105105"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202100237"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2016.1257807"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201900113"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c05519"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060655"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2021.105621"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt540"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21863"},{"key":"e_1_2_7_21_1","first-page":"49","article-title":"Design, Synthesis and In Silico Evaluation of Benzotriazole\u2010Based Urea Derivatives as Potential VEGFR\u20102 Inhibitors","volume":"3","author":"Hassan M. 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