{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:04:37Z","timestamp":1790305477632,"version":"4.1.0"},"reference-count":87,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["ORF-2026-1994"],"award-info":[{"award-number":["ORF-2026-1994"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.bmc.2026.118766","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:58:33Z","timestamp":1785772713000},"page":"118766","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Novel benzofuran\u20131,3,4-thiadiazole aryl urea hybrids as dual VEGFR-2\/BRAF inhibitors: anticancer activity, apoptosis induction, and molecular modeling studies"],"prefix":"10.1016","volume":"142","author":[{"given":"Marwa I.","family":"Serag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed R.","family":"Elnagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa A.","family":"Ewes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A.-M.","family":"Abdel-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem A.","family":"Ghabbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiby N.","family":"Takla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Hamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed W.","family":"El-Shafey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel S.","family":"El-Azab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2026.118766_bb0005","article-title":"Mechanisms of angiogenesis in tumour","volume":"14\u20132024","author":"Zhang","year":"2024","journal-title":"Front Oncol"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0010","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41392-025-02249-0","article-title":"Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives","volume":"10","author":"Lee","year":"2025","journal-title":"Signal Transduct Target Ther"},{"issue":"5","key":"10.1016\/j.bmc.2026.118766_bb0015","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s12272-025-01545-1","article-title":"Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance","volume":"48","author":"Shah","year":"2025","journal-title":"Arch Pharm Res"},{"issue":"9","key":"10.1016\/j.bmc.2026.118766_bb0020","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1080\/1061186X.2025.2508985","article-title":"Revisiting VEGF\/VEGFR-2 signalling as an anticancer target and its inhibitor discovery: where are we and where should we go?","volume":"33","author":"Yao","year":"2025","journal-title":"J Drug Target"},{"key":"10.1016\/j.bmc.2026.118766_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.medidd.2019.100009","article-title":"Vascular endothelial growth factor receptor (VEGFR-2)\/KDR inhibitors: medicinal chemistry perspective","volume":"2","author":"Modi","year":"2019","journal-title":"Med Drug Discov"},{"issue":"22","key":"10.1016\/j.bmc.2026.118766_bb0030","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29225341","article-title":"Targeting vascular endothelial growth factor receptor 2 (VEGFR-2): latest insights on synthetic strategies","volume":"29","author":"Marques","year":"2024","journal-title":"Molecules"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.gendis.2022.05.006","article-title":"Targeting RAS\u2013RAF\u2013MEK\u2013ERK signaling pathway in human cancer: current status in clinical trials","volume":"10","author":"Song","year":"2023","journal-title":"Genes Dis."},{"issue":"8","key":"10.1016\/j.bmc.2026.118766_bb0040","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.bbamcr.2007.05.001","article-title":"Raf kinases: function, regulation and role in human cancer","volume":"1773","author":"Leicht","year":"2007","journal-title":"Biochim Biophys Acta"},{"issue":"32","key":"10.1016\/j.bmc.2026.118766_bb0045","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1038\/onc.2011.160","article-title":"Raf kinases in cancer\u2013roles and therapeutic opportunities","volume":"30","author":"Maurer","year":"2011","journal-title":"Oncogene"},{"issue":"5","key":"10.1016\/j.bmc.2026.118766_bb0050","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0898-6568(02)00139-0","article-title":"Mechanisms of regulating the Raf kinase family","volume":"15","author":"Chong","year":"2003","journal-title":"Cell Signal"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0055","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3390\/receptors3010005","article-title":"Role and function of receptor tyrosine kinases in BRAF mutant cancers","volume":"3","author":"Biersack","year":"2024","journal-title":"Receptors"},{"issue":"4","key":"10.1016\/j.bmc.2026.118766_bb0060","first-page":"431","article-title":"Targeting BRAF in cancers - from molecular diagnostics to personalized therapy","volume":"106","author":"Pyc","year":"2025","journal-title":"BioTechnol (Pozn)"},{"key":"10.1016\/j.bmc.2026.118766_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.medidd.2025.100234","article-title":"Molecular strategies in BRAF targeting: advances in patents, structure activity relationship and future prospects","volume":"28","author":"Saha","year":"2025","journal-title":"Med Drug Discov"},{"issue":"8","key":"10.1016\/j.bmc.2026.118766_bb0070","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.3390\/ijms26083757","article-title":"BRAF targeting across solid tumors: molecular aspects and clinical applications","volume":"26","author":"Mechahougui","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"2","key":"10.1016\/j.bmc.2026.118766_bb0075","doi-asserted-by":"crossref","first-page":"371","DOI":"10.62347\/IRQS3605","article-title":"BRAF mutation and tumor immune microenvironment in new era","volume":"16","author":"Zhou","year":"2026","journal-title":"Am J Cancer Res"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0080","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/1535370220959657","article-title":"Prevalence of class I\u2013III BRAF mutations among 114,662 cancer patients in a large genomic database","volume":"246","author":"Owsley","year":"2021","journal-title":"Exp Biol Med"},{"key":"10.1016\/j.bmc.2026.118766_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108526","article-title":"Design and synthesis of novel 2-S-alkylated quinazolinones as dual BRAFV600E and EGFR inhibitors in melanoma: mechanistic insights from apoptosis and cell cycle modulation","volume":"161","author":"El-Shafey","year":"2025","journal-title":"Bioorg Chem"},{"issue":"6","key":"10.1016\/j.bmc.2026.118766_bb0090","article-title":"Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations","volume":"5","author":"Wang","year":"2024","journal-title":"Innovation"},{"issue":"19","key":"10.1016\/j.bmc.2026.118766_bb0095","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1158\/0008-5472.CAN-04-1443","article-title":"BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF\/MEK\/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis","volume":"64","author":"Wilhelm","year":"2004","journal-title":"Cancer Res"},{"issue":"5","key":"10.1016\/j.bmc.2026.118766_bb0100","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1007\/s10620-012-2136-1","article-title":"Sorafenib for treatment of hepatocellular carcinoma: a systematic review","volume":"57","author":"Xie","year":"2012","journal-title":"Dig Dis Sci"},{"issue":"24","key":"10.1016\/j.bmc.2026.118766_bb0105","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1158\/1078-0432.CCR-06-1249","article-title":"Sorafenib for the treatment of advanced renal cell carcinoma","volume":"12","author":"Kane","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0110","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ijc.25864","article-title":"Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity","volume":"129","author":"Wilhelm","year":"2011","journal-title":"Int J Cancer"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0115","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s10637-012-9845-3","article-title":"RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications","volume":"31","author":"Garcia-Gomez","year":"2013","journal-title":"Investig New Drugs"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0120","first-page":"253","article-title":"Understanding and targeting resistance to anti-angiogenic therapies","volume":"4","author":"Clarke","year":"2013","journal-title":"J Gastrointest Oncol"},{"key":"10.1016\/j.bmc.2026.118766_bb0125","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.phrs.2015.10.021","article-title":"Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes","volume":"103","author":"Roskoski","year":"2016","journal-title":"Pharmacol Res"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0130","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1021\/jm0608107","article-title":"Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors","volume":"50","author":"Liao","year":"2007","journal-title":"J Med Chem"},{"issue":"7","key":"10.1016\/j.bmc.2026.118766_bb0135","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tips.2015.04.005","article-title":"FDA-approved small-molecule kinase inhibitors","volume":"36","author":"Wu","year":"2015","journal-title":"Trends Pharmacol Sci"},{"issue":"13","key":"10.1016\/j.bmc.2026.118766_bb0140","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29133186","article-title":"Identification of benzothiazoles bearing 1,3,4-thiadiazole as antiproliferative hybrids targeting VEGFR-2 and BRAF kinase: design, synthesis, BIO evaluation and in silico study","volume":"29","author":"Ewes","year":"2024","journal-title":"Molecules"},{"key":"10.1016\/j.bmc.2026.118766_bb0145","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ejmech.2019.06.063","article-title":"Novel potent substituted 4-amino-2-thiopyrimidines as dual VEGFR-2 and BRAF kinase inhibitors","volume":"179","author":"Abdel-Mohsen","year":"2019","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2026.118766_bb0150","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ejmech.2014.10.085","article-title":"Biological and medicinal significance of benzofuran","volume":"97","author":"Nevagi","year":"2015","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmc.2026.118766_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2023.137098","article-title":"Furan and benzofuran derivatives as privileged scaffolds as anticancer agents: SAR and docking studies (2010 to till date)","volume":"1299","author":"Patel","year":"2024","journal-title":"J Mol Struct"},{"issue":"16","key":"10.1016\/j.bmc.2026.118766_bb0160","doi-asserted-by":"crossref","first-page":"11096","DOI":"10.1039\/D3RA01383A","article-title":"Anticancer therapeutic potential of benzofuran scaffolds","volume":"13","author":"Abbas","year":"2023","journal-title":"RSC Adv"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0165","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/jhet.3795","article-title":"Benzofuran-isatin conjugates as potent VEGFR-2 and cancer cell growth inhibitors","volume":"57","author":"Zou","year":"2020","journal-title":"J Heterocyclic Chem"},{"issue":"23","key":"10.1016\/j.bmc.2026.118766_bb0170","doi-asserted-by":"crossref","first-page":"11569","DOI":"10.1039\/c4ra00943f","article-title":"Design, synthesis and anticancer activity of benzofuran derivatives targeting VEGFR-2 tyrosine kinase","volume":"4","author":"Abdelhafez","year":"2014","journal-title":"RSC Adv"},{"key":"10.1016\/j.bmc.2026.118766_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103035","article-title":"Design, synthesis and anticervical cancer activity of new benzofuran\u2013pyrazol-hydrazono- thiazolidin-4-one hybrids as potential EGFR inhibitors and apoptosis inducing agents","volume":"89","author":"Abbas","year":"2019","journal-title":"Bioorg Chem"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0180","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1080\/14756366.2018.1510919","article-title":"Benzofuran\u2013appended 4-aminoquinazoline hybrids as epidermal growth factor receptor tyrosine kinase inhibitors: synthesis, biological evaluation and molecular docking studies","volume":"33","author":"Mphahlele","year":"2018","journal-title":"J Enzyme Inhibit Med Chem"},{"issue":"21","key":"10.1016\/j.bmc.2026.118766_bb0185","doi-asserted-by":"crossref","first-page":"30624","DOI":"10.1021\/acsomega.5c12128","article-title":"Khellin-derived benzofuran\u2013pyrazoline hybrids as kinase-targeted anticancer agents","volume":"11","author":"Al-Qadhi","year":"2026","journal-title":"ACS Omega"},{"issue":"42","key":"10.1016\/j.bmc.2026.118766_bb0190","doi-asserted-by":"crossref","first-page":"35003","DOI":"10.1039\/D5RA00553A","article-title":"Design, synthesis, and in silico studies of new benzofuran-pyrazole hybrids as multi-kinase inhibitors with potential antiproliferative activity","volume":"15","author":"Abd El-Karim","year":"2025","journal-title":"RSC Adv"},{"key":"10.1016\/j.bmc.2026.118766_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108702","article-title":"Triazole-functionalized benzofuran and benzothiophene semicarbazides as novel VEGFR-2-targeted anti-cancer agents","volume":"163","author":"Nafie","year":"2025","journal-title":"Bioorg Chem"},{"issue":"2","key":"10.1016\/j.bmc.2026.118766_bb0200","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1039\/D5MD01043H","article-title":"Discovery of enaminone-linked benzofuran derivatives as dual VEGFR-2\/hCA IX inhibitors exhibiting hypoxia-mediated chemosensitization","volume":"17","author":"Eldehna","year":"2026","journal-title":"RSC Med Chem"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0205","doi-asserted-by":"crossref","first-page":"17104","DOI":"10.1038\/s41598-022-21277-2","article-title":"Design, synthesis and computational study of new benzofuran hybrids as dual PI3K\/VEGFR2 inhibitors targeting cancer","volume":"12","author":"El-Khouly","year":"2022","journal-title":"Sci Rep"},{"issue":"4","key":"10.1016\/j.bmc.2026.118766_bb0210","doi-asserted-by":"crossref","DOI":"10.1002\/cbdv.202401991","article-title":"Benzofuran-chalcone derivatives as VEGFR-2 inhibitors: synthesis and anticancer evaluation","volume":"22","author":"Liu","year":"2025","journal-title":"Chem Biodivers"},{"key":"10.1016\/j.bmc.2026.118766_bb0215","article-title":"A novel benzofuran derivative moracin N induces autophagy and apoptosis through ROS generation in lung cancer","volume":"11\u20132020","author":"Gao","year":"2020","journal-title":"Front Pharmacol"},{"issue":"12","key":"10.1016\/j.bmc.2026.118766_bb0220","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.4161\/15384047.2014.964087","article-title":"Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy","volume":"15","author":"Sun","year":"2014","journal-title":"Cancer Biol Ther"},{"issue":"16","key":"10.1016\/j.bmc.2026.118766_bb0225","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1007\/s40265-018-0998-z","article-title":"Fruquintinib: first global approval","volume":"78","author":"Shirley","year":"2018","journal-title":"Drugs"},{"key":"10.1016\/j.bmc.2026.118766_bb0230","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116124","article-title":"Synthesis and clinical application of new drugs approved by FDA in 2023","volume":"265","author":"Wang","year":"2024","journal-title":"Eur J Med Chem"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0235","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00280-016-2958-1","article-title":"A pharmacodynamically guided dose selection of PF-00337210 in a phase I study in patients with advanced solid tumors","volume":"77","author":"Bruce","year":"2016","journal-title":"Cancer Chemother Pharmacol"},{"issue":"9_Supplement","key":"10.1016\/j.bmc.2026.118766_bb0240","first-page":"3992","article-title":"PF-00337210, a potent, selective and orally bioavailable small molecule inhibitor of VEGFR-2","volume":"67","author":"Marrone","year":"2007","journal-title":"Cancer Res"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0245","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/14756366.2021.1915302","article-title":"Development of 3-methyl\/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells","volume":"36","author":"Al-Sanea","year":"2021","journal-title":"J Enzyme Inhibit Med Chem"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0250","doi-asserted-by":"crossref","DOI":"10.1080\/14756366.2023.2166036","article-title":"New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study","volume":"38","author":"Al-Sanea","year":"2023","journal-title":"J Enzyme Inhib Med Chem"},{"key":"10.1016\/j.bmc.2026.118766_bb0255","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.2147\/DDDT.S490930","article-title":"Design, synthesis, pharmacological evaluation of quinazolin-4(3H)-ones bearing urea functionality as potential VEGFR-2 inhibitors","volume":"18","author":"Al-Sanea","year":"2024","journal-title":"Drug Des Devel Ther"},{"key":"10.1016\/j.bmc.2026.118766_bb0260","first-page":"1","article-title":"Quinazoline-sulfonamide hybrids as multitarget anticancer agents: inhibition of carbonic anhydrase IX\/XII isoforms and VEGFR-2 with in vitro and in silico validation","author":"Zeidan","year":"2026","journal-title":"Mol Divers"},{"issue":"23","key":"10.1016\/j.bmc.2026.118766_bb0265","doi-asserted-by":"crossref","first-page":"21079","DOI":"10.1039\/D5RA09370H","article-title":"Discovery of thieno[2,3-d]pyrimidine-based dual Aurora B\/VEGFR-2 inhibitors with potent anticancer activity: molecular docking, mechanistic studies, and in vivo validation in a breast cancer model","volume":"16","author":"El-Shafey","year":"2026","journal-title":"RSC Adv"},{"issue":"9","key":"10.1016\/j.bmc.2026.118766_bb0270","doi-asserted-by":"crossref","first-page":"16566","DOI":"10.3390\/molecules200916566","article-title":"Benzofuranyl esters: synthesis, crystal structure determination, antimicrobial and antioxidant activities","volume":"20","author":"Kumar","year":"2015","journal-title":"Molecules"},{"issue":"13","key":"10.1016\/j.bmc.2026.118766_bb0275","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29133186","article-title":"Identification of benzothiazoles bearing 1, 3, 4-thiadiazole as antiproliferative hybrids targeting VEGFR-2 and BRAF kinase: design, synthesis, BIO evaluation and in silico study","volume":"29","author":"Ewes","year":"2024","journal-title":"Molecules"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0280","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.28612","article-title":"Targeting the multifaceted BRAF in cancer: new directions","volume":"15","author":"Toye","year":"2024","journal-title":"Oncotarget"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0285","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0059221","article-title":"Automated universal BRAF state detection within the activation segment in skin metastases by pyrosequencing-based assay U-BRAFV600","volume":"8","author":"Skorokhod","year":"2013","journal-title":"PLoS One"},{"issue":"6892","key":"10.1016\/j.bmc.2026.118766_bb0290","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.bmc.2026.118766_bb0295","first-page":"1486","article-title":"BRAF(V600E) mutation promoted the growth and chemoresistance of colorectal cancer","volume":"13","author":"Ma","year":"2023","journal-title":"Am J Cancer Res"},{"issue":"5","key":"10.1016\/j.bmc.2026.118766_bb0300","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ebiom.2015.03.021","article-title":"MET suppresses epithelial VEGFR2 via intracrine VEGF-induced endoplasmic reticulum-associated degradation","volume":"2","author":"Chen","year":"2015","journal-title":"EBioMedicine"},{"issue":"2","key":"10.1016\/j.bmc.2026.118766_bb0305","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1210\/me.2007-0319","article-title":"Vascular endothelial growth factor receptor-2 expression is down-regulated by 17beta-estradiol in MCF-7 breast cancer cells by estrogen receptor alpha\/Sp proteins","volume":"22","author":"Higgins","year":"2008","journal-title":"Mol Endocrinol"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0310","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1186\/s12885-017-3578-9","article-title":"VEGFR2 regulates endothelial differentiation of colon cancer cells","volume":"17","author":"Liu","year":"2017","journal-title":"BMC Cancer"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0315","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3892\/mmr.2020.11700","article-title":"Hyperoxia sensitizes hypoxic HeLa cells to ionizing radiation by downregulating HIF-1\u03b1 and VEGF expression","volume":"23","author":"Dong","year":"2021","journal-title":"Mol Med Rep"},{"issue":"1\u20132","key":"10.1016\/j.bmc.2026.118766_bb0320","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"10.1016\/j.bmc.2026.118766_bb0325","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107234","article-title":"New 2-oxoindole derivatives as multiple PDGFR\u03b1\/\u00df and VEGFR-2 tyrosine kinase inhibitors","volume":"145","author":"Ezelarab","year":"2024","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2026.118766_bb0330","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.106099","article-title":"Design and synthesis of some new 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines as multi tyrosine kinase inhibitors","volume":"128","author":"Farouk","year":"2022","journal-title":"Bioorg Chem"},{"key":"10.1016\/j.bmc.2026.118766_bb0335","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2026.109846","article-title":"Click chemistry synthesis of triazole-grafted quinazolinones as new multi-panel anticancer agents: mechanistic insights into apoptosis and cell cycle arrest in colorectal cancer","volume":"176","author":"Al-Sanea","year":"2026","journal-title":"Bioorg Chem"},{"issue":"null","key":"10.1016\/j.bmc.2026.118766_bb0340","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.2147\/DDDT.S490930","article-title":"Design, synthesis, pharmacological evaluation of quinazolin-4(3H)-ones bearing urea functionality as potential VEGFR-2 inhibitors","volume":"18","author":"Al-Sanea","year":"2024","journal-title":"Drug Des Devel Ther"},{"issue":"16","key":"10.1016\/j.bmc.2026.118766_bb0345","doi-asserted-by":"crossref","first-page":"9442","DOI":"10.3390\/ijms23169442","article-title":"Augmented therapeutic potential of EC-synthetic retinoids in Caco-2 Cancer cells using an In vitro approach","volume":"23","author":"Abdelaal","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"15","key":"10.1016\/j.bmc.2026.118766_bb0350","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2020.127281","article-title":"Quinazoline based HSP90 inhibitors: synthesis, modeling study and ADME calculations towards breast Cancer targeting","volume":"30","author":"El-Shafey","year":"2020","journal-title":"Bioorg Med Chem Lett"},{"issue":"12","key":"10.1016\/j.bmc.2026.118766_bb0355","doi-asserted-by":"crossref","DOI":"10.3390\/ph18121875","article-title":"Discovery of novel piperidinyl-based benzoxazole derivatives as anticancer agents targeting VEGFR-2 and c-Met kinases","volume":"18","author":"Eldehna","year":"2025","journal-title":"Pharmaceuticals (Basel)"},{"key":"10.1016\/j.bmc.2026.118766_bb0360","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.109263","article-title":"New 2-benzylideneamino-4,5-diphenylfuran-3-carbonitrile derivatives and their benzylamino analogues: synthesis, in vitro cytotoxicity, protein kinase inhibitory activity and in silico insights","volume":"168","author":"Osman","year":"2026","journal-title":"Bioorg Chem"},{"issue":"45","key":"10.1016\/j.bmc.2026.118766_bb0365","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J Am Chem Soc"},{"issue":"11","key":"10.1016\/j.bmc.2026.118766_bb0370","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1021\/acsmedchemlett.0c00395","article-title":"Spiroindoline-capped selective HDAC6 inhibitors: Design, synthesis, structural analysis, and biological evaluation","volume":"11","author":"Saraswati","year":"2020","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmc.2026.118766_bb0375","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ejmech.2018.11.004","article-title":"Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents","volume":"162","author":"Brindisi","year":"2019","journal-title":"Eur J Med Chem"},{"issue":"6","key":"10.1016\/j.bmc.2026.118766_bb0380","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1039\/C9FO00265K","article-title":"Dietary polyphenols rutin, taxifolin and quercetin related compounds target Leishmania amazonensis arginase","volume":"10","author":"da Silva","year":"2019","journal-title":"Food Funct"},{"key":"10.1016\/j.bmc.2026.118766_bb0385","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ejmech.2017.04.057","article-title":"Structural characterization of Giardia duodenalis thioredoxin reductase (gTrxR) and computational analysis of its interaction with NBDHEX","volume":"135","author":"Brogi","year":"2017","journal-title":"Eur J Med Chem"},{"issue":"7","key":"10.1016\/j.bmc.2026.118766_bb0390","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J Med Chem"},{"issue":"2","key":"10.1016\/j.bmc.2026.118766_bb0395","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"key":"10.1016\/j.bmc.2026.118766_bb0400","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112998","article-title":"Novel quinolone-based potent and selective HDAC6 inhibitors: synthesis, molecular modeling studies and biological investigation","volume":"212","author":"Relitti","year":"2021","journal-title":"Eur J Med Chem"},{"issue":"9","key":"10.1016\/j.bmc.2026.118766_bb0405","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1039\/D0FO01511C","article-title":"Amyloid \u03b2 fibril disruption by oleuropein aglycone: long-time molecular dynamics simulation to gain insight into the mechanism of action of this polyphenol from extra virgin olive oil","volume":"11","author":"Brogi","year":"2020","journal-title":"Food Funct"},{"issue":"27","key":"10.1016\/j.bmc.2026.118766_bb0410","doi-asserted-by":"crossref","first-page":"6885","DOI":"10.1021\/j100078a035","article-title":"A multiple-time-step molecular dynamics algorithm for macromolecules","volume":"98","author":"Humphreys","year":"1994","journal-title":"J Phys Chem"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0415","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical dynamics: equilibrium phase-space distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys Rev A"},{"issue":"5","key":"10.1016\/j.bmc.2026.118766_bb0420","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant pressure molecular dynamics algorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J Chem Phys"},{"issue":"19","key":"10.1016\/j.bmc.2026.118766_bb0425","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J Chem Phys"},{"issue":"3","key":"10.1016\/j.bmc.2026.118766_bb0430","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s11030-023-10650-6","article-title":"Discovery of novel direct small-molecule inhibitors targeting HIF-2\u03b1 using structure-based virtual screening, molecular dynamics simulation, and MM-GBSA calculations","volume":"28","author":"Yazdani","year":"2024","journal-title":"Mol Divers"},{"issue":"1","key":"10.1016\/j.bmc.2026.118766_bb0435","doi-asserted-by":"crossref","DOI":"10.1007\/s10822-026-00865-8","article-title":"Integrated structure-based and fragment-guided design of isonicotinic acid derivatives as potential KDM4A inhibitors: an in silico study","volume":"40","author":"Eslami","year":"2026","journal-title":"J Comput Aided Mol Des"}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089626002221?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089626002221?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:37:39Z","timestamp":1788597459000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089626002221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":87,"alternative-id":["S0968089626002221"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2026.118766","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel benzofuran\u20131,3,4-thiadiazole aryl urea hybrids as dual VEGFR-2\/BRAF inhibitors: anticancer activity, apoptosis induction, and molecular modeling studies","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2026.118766","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118766"}}