{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:07:34Z","timestamp":1791828454209,"version":"4.3.4"},"reference-count":62,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002657","name":"Istanbul \u00dcniversitesi","doi-asserted-by":"publisher","award":["36598"],"award-info":[{"award-number":["36598"]}],"id":[{"id":"10.13039\/501100002657","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002657","name":"Istanbul \u00dcniversitesi","doi-asserted-by":"publisher","award":["24778"],"award-info":[{"award-number":["24778"]}],"id":[{"id":"10.13039\/501100002657","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004006","name":"Istanbul University Scientific Research Projects Unit","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["122S051"],"award-info":[{"award-number":["122S051"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.ejmech.2025.118509","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T17:06:23Z","timestamp":1766163983000},"page":"118509","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Novel 1-benzyl-2-indolinone indole hybrids as tyrosine kinase inhibitors: Design, synthesis, and biological activity evaluation"],"prefix":"10.1016","volume":"304","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-6010","authenticated-orcid":false,"given":"G\u00f6k\u00e7e","family":"Cihan-\u00dcst\u00fcnda\u011f","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011f\u00e7e","family":"Cinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serap","family":"Sancar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oykum","family":"Genc-Akar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcne\u015f","family":"\u00d6zen-Ero\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Erol-Bozkurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusun","family":"Oztay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge","family":"Soylu-Eter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehnaz","family":"Bolkent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serap","family":"Kuruca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilg\u00fcn","family":"Karal\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.118509_bib1","doi-asserted-by":"crossref","DOI":"10.1186\/s12943-018-0782-4","article-title":"Mechanisms of receptor tyrosine kinase activation in cancer","volume":"17","author":"Du","year":"2018","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.ejmech.2025.118509_bib2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7150\/ijms.1.101","article-title":"Tyrosine kinase-role and significance in cancer","volume":"1","author":"Paul","year":"2004","journal-title":"Int. J. Med. Sci."},{"key":"10.1016\/j.ejmech.2025.118509_bib3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4236\/pp.2012.31010","article-title":"Indolin-2-ones in clinical trials as potential kinase \u0131nhibitors: a review","volume":"3","author":"Prakash","year":"2012","journal-title":"Pharmacol. Pharm."},{"key":"10.1016\/j.ejmech.2025.118509_bib4","first-page":"99","article-title":"SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1\/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types","volume":"59","author":"Annie","year":"1999","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118509_bib5","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.tiv.2005.06.047","article-title":"Distribution, metabolism, and excretion of the anti-angiogenic compound SU5416","volume":"20","author":"Ye","year":"2006","journal-title":"Toxicol. Vitro"},{"key":"10.1016\/j.ejmech.2025.118509_bib6","first-page":"4152","article-title":"SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors","volume":"60","author":"Laird","year":"2000","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118509_bib7","first-page":"1142","article-title":"Su-6668. SUGEN","volume":"2","author":"Fabbro","year":"2001","journal-title":"Curr. Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2025.118509_bib8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1634\/theoncologist.2016-0197","article-title":"Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma","volume":"22","author":"Motzer","year":"2017","journal-title":"Oncologist"},{"key":"10.1016\/j.ejmech.2025.118509_bib9","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2147\/tcrm.2007.3.2.341","article-title":"Sunitinib: a novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors (GIST)","volume":"3","author":"Le Tourneau","year":"2007","journal-title":"Therapeut. Clin. Risk Manag."},{"key":"10.1016\/j.ejmech.2025.118509_bib10","article-title":"Predictive immunohistochemical markers related to drug selection for patients treated with sunitinib or sorafenib for metastatic renal cell cancer","volume":"6","author":"Ma","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2025.118509_bib11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s40268-017-0221-9","article-title":"Efficacy and safety of nintedanib for the treatment of idiopathic pulmonary fibrosis: an update","volume":"18","author":"Rodr\u00edguez-Portal","year":"2018","journal-title":"Drugs R&D"},{"key":"10.1016\/j.ejmech.2025.118509_bib12","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ejmech.2019.01.049","article-title":"Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents","volume":"166","author":"Morigi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2020.127355","article-title":"Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells","volume":"30","author":"Yao","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2025.118509_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.113083","article-title":"Design, synthesis, and in vitro and in vivo anti-angiogenesis study of a novel vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor based on 1,2,3-triazole scaffold","volume":"211","author":"Wang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib15","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1021\/jm011123c","article-title":"Synthesis and antitumor activity of 1,5,6-substituted E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones","volume":"45","author":"Andreani","year":"2002","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib16","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.bmc.2003.11.031","article-title":"Substituted E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity","volume":"12","author":"Andreani","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib17","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1021\/jm1007165","article-title":"Substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones with antitumor activity. In depth study of the effect on growth of breast cancer cells 1","volume":"53","author":"Andreani","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib18","doi-asserted-by":"crossref","first-page":"4968","DOI":"10.1016\/j.ejmech.2010.08.004","article-title":"Synthesis and evaluation of indole, pyrazole, chromone, and pyrimidine based conjugates for tumor growth \u0131nhibitory activities-development of highly efficacious cytotoxic agents","volume":"45","author":"Singh","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib19","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.ejmech.2014.04.004","article-title":"Substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones with antiproliferative activity. Study of the effects on HL-60 leukemia cells","volume":"79","author":"Leoni","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108203","article-title":"New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors","volume":"156","author":"Camc\u0131-Eren","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib21","unstructured":"N. Karal\u0131, G. Cihan-\u00dcst\u00fcnda\u011f, New 3-arylidene-2-indolinone Derivatives, TR 2020 04769 B."},{"key":"10.1016\/j.ejmech.2025.118509_bib22","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1016\/j.bmc.2017.05.029","article-title":"Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases","volume":"25","author":"Karal\u0131","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.104202","article-title":"Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones","volume":"104","author":"Sevin\u00e7li","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib24","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1021\/jm980123i","article-title":"Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases","volume":"41","author":"Sun","year":"1998","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib25","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1016\/j.bmc.2008.02.093","article-title":"Synthesis of 1-substituted 3-pyridinylmethylidenylindolin-2-ones and 1-substituted 3-quinolinylmethylidenylindolin-2-ones as the enhancers of atra-induced differentiation in HL-60 cells","volume":"16","author":"Hung","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib26","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1517\/14656566.8.14.2359","article-title":"Sunitinib","volume":"8","author":"Rini","year":"2007","journal-title":"Expet Opin. Pharmacother."},{"key":"10.1016\/j.ejmech.2025.118509_bib27","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nrd2380","article-title":"Molecular basis for sunitinib efficacy and future clinical development","volume":"6","author":"Faivre","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2025.118509_bib28","first-page":"327","article-title":"In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic\/pharmacodynamic relationship","volume":"9","author":"Mendel","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118509_bib29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10456-004-3149-y","article-title":"The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels","volume":"7","author":"Osusky","year":"2004","journal-title":"Angiogenesis"},{"key":"10.1016\/j.ejmech.2025.118509_bib30","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1186\/1471-2407-14-939","article-title":"Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib","volume":"14","author":"Fiorio Pla","year":"2014","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ejmech.2025.118509_bib31","doi-asserted-by":"crossref","first-page":"511","DOI":"10.4149\/gpb_2015055","article-title":"Inhibition of VEGF mediated post receptor signalling pathways by recently developed tyrosine kinase inhibitor in comparison with sunitinib","volume":"35","author":"Morav\u010d\u00edk","year":"2016","journal-title":"Gen. Physiol. Biophys."},{"key":"10.1016\/j.ejmech.2025.118509_bib32","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.3390\/biomedicines9111630","article-title":"Antiangiogenic properties of axitinib versus sorafenib following sunitinib resistance in human endothelial cells-A view towards second line renal cell carcinoma treatment","volume":"9","author":"Juengel","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.ejmech.2025.118509_bib33","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ijbiomac.2021.03.075","article-title":"Role of receptor tyrosine kinases mediated signal transduction pathways in tumor growth and angiogenesis\u2014New insight and futuristic vision","volume":"180","author":"Huang","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejmech.2025.118509_bib34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3892\/or.2020.7859","article-title":"Platelet-derived growth factor-BB mediates pancreatic cancer malignancy via regulation of the Hippo\/yes-associated protein signaling pathway","volume":"45","author":"Li","year":"2021","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejmech.2025.118509_bib35","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3349\/ymj.2018.59.6.727","article-title":"Synergistic anti-cancer effects of AKT and Src inhibition in human pancreatic cancer cells","volume":"59","author":"Ahn","year":"2018","journal-title":"Yonsei Med. J."},{"key":"10.1016\/j.ejmech.2025.118509_bib36","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2011.08.009","article-title":"c-Met is a marker of pancreatic cancer stem cells and therapeutic target","volume":"141","author":"Li","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejmech.2025.118509_bib37","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.3390\/cancers17101607","article-title":"Unraveling the burden of pancreatic cancer in the 21st century: trends in incidence, mortality, survival, and key contributing factors","volume":"17","author":"Zottl","year":"2025","journal-title":"Cancers"},{"key":"10.1016\/j.ejmech.2025.118509_bib38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ymthe.2022.11.004","article-title":"Imatinib facilitates gemcitabine sensitivity by targeting epigenetically activated PDGFC signaling in pancreatic cancer","volume":"31","author":"Shi","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ejmech.2025.118509_bib39","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1158\/1078-0432.CCR-05-1571","article-title":"Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer","volume":"12","author":"Siu","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.118509_bib40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11523-020-00784-0","article-title":"Updated efficacy and safety outcomes for patients with well-differentiated pancreatic neuroendocrine tumors treated with sunitinib","volume":"16","author":"Fazio","year":"2021","journal-title":"Targeted Oncol."},{"key":"10.1016\/j.ejmech.2025.118509_bib41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.canlet.2019.05.025","article-title":"AKT and ERK dual inhibitors: the way forward","volume":"459","author":"Cao","year":"2019","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ejmech.2025.118509_bib42","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/jcb.10287","article-title":"Frequent activation of AKT2 kinase in human pancreatic carcinomas","volume":"87","author":"Altomare","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.ejmech.2025.118509_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109383","article-title":"Inhibition of AKT enhances the anti-cancer effects of artemisinin in clear cell renal cell carcinoma","volume":"118","author":"Yu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2025.118509_bib44","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.3390\/cancers13123026","article-title":"MAPK\/ERK signaling pathway in hepatocellular carcinoma","volume":"13","author":"Moon","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.ejmech.2025.118509_bib45","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.taap.2013.01.011","article-title":"Inhibition of AKT enhances mitotic cell apoptosis induced by arsenic trioxide","volume":"267","author":"Yih","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.118509_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2021.103074","article-title":"Characteristic ERK1\/2 signaling dynamics distinguishes necroptosis from apoptosis","volume":"24","author":"Sipieter","year":"2021","journal-title":"iScience"},{"key":"10.1016\/j.ejmech.2025.118509_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0106225","article-title":"c-Src binds to the cancer drug Ruxolitinib with an active conformation","volume":"9","author":"Duan","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.118509_bib48","doi-asserted-by":"crossref","unstructured":"L. Liang, X.E. Yan, C.H. Yun, Crystal structure of PDGFRA in complex with sunitinib by soaking, https:\/\/doi.org\/10.2210\/pdb6JOK\/pdb.","DOI":"10.2210\/pdb6jok\/pdb"},{"key":"10.1016\/j.ejmech.2025.118509_bib49","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1074\/jbc.M705774200","article-title":"c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations","volume":"283","author":"Bellon","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib50","doi-asserted-by":"crossref","first-page":"18872","DOI":"10.1021\/acsomega.0c02038","article-title":"Dual targeting of VEGFR2 and c-Met kinases via the design and synthesis of substituted 3-(triazolo-thiadiazin-3-yl)indolin-2-one derivatives as angiogenesis inhibitors","volume":"5","author":"Mohamady","year":"2020","journal-title":"ACS Omega"},{"key":"10.1016\/j.ejmech.2025.118509_bib51","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejmech.2025.118509_bib52","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1367-5931(00)00226-X","article-title":"Drug delivery: an odyssey of 100 years","volume":"5","author":"Pillai","year":"2001","journal-title":"Curr. Opin. Chem. Biol."},{"key":"10.1016\/j.ejmech.2025.118509_bib53","doi-asserted-by":"crossref","first-page":"9889","DOI":"10.1016\/j.tet.2004.08.030","article-title":"Application of a catalytic palladium biaryl synthesis reaction, via C-H functionalization, to the total synthesis of amaryllidaceae alkaloids","volume":"60","author":"Torres","year":"2004","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2025.118509_bib54","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1021\/jm0704189","article-title":"An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins","volume":"50","author":"Vine","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib55","series-title":"New 1-substituted 1H-indole-2,3-dione Compounds and Synthesis Methods","author":"Karal\u0131","year":"2015"},{"key":"10.1016\/j.ejmech.2025.118509_bib56","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1021\/ol800141t","article-title":"Palladium-catalyzed \u03b1-arylation of oxindoles","volume":"10","author":"Durbin","year":"2008","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2025.118509_bib57","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1039\/C8OB02859A","article-title":"Palladium-catalysed ring-opening [3+2]-annulation of spirovinylcyclopropyl oxindole to diastereoselectively access spirooxindoles","volume":"17","author":"Xiao","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib58","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1016\/j.bmc.2013.01.047","article-title":"Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) \u0131nhibitors: molecular docking simulation and structure-activity relationship analysis","volume":"21","author":"Zhong","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib59","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.bmc.2010.01.011","article-title":"Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors","volume":"18","author":"Mologni","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.118509_bib60","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.ejmech.2025.118509_bib61","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/jcb.29920","article-title":"Effect of long noncoding RNAs on epithelial\u2013mesenchymal transition in A549 cells and fibrotic human lungs","volume":"122","author":"Yildirim","year":"2021","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.ejmech.2025.118509_bib62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-60327-017-5_2","article-title":"Flow cytometry-based apoptosis detection","volume":"559","author":"Wlodkowic","year":"2009","journal-title":"Methods Mol. Biol."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012747?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425012747?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:11:49Z","timestamp":1778735509000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425012747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":62,"alternative-id":["S0223523425012747"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118509","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel 1-benzyl-2-indolinone indole hybrids as tyrosine kinase inhibitors: Design, synthesis, and biological activity evaluation","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.118509","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118509"}}