{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:06:24Z","timestamp":1789027584986,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aberrant activation of Aurora A kinase causes mitotic spindle assembly, chromosome segregation, and cell cycle progression, leading to genomic instability as well as disruption of several tumor suppressors. Furthermore, ERK has largely emerged as a survival signaling pathway controlling cell proliferation, differentiation, and metastasis. Unfortunately, this pathway is overexpressed in most of the human malignancies. In efforts to develop innovative inhibitors targeting Aurora A\/ERK signaling pathway, a novel series of thiadiazolo\u2010, triazolo\u2010pyrimidine hybrids have been designed, synthesized, and assessed for their ability to block Aurora A\/ERK and induce apoptosis. Cytotoxicity of the synthesized hybrids was examined against MCF\u20107, HCT\u2010116 and A549 cell lines. Among the synthesized hybrids,\n                    <jats:bold>9a<\/jats:bold>\n                    ,\n                    <jats:bold>9c<\/jats:bold>\n                    , and\n                    <jats:bold>14b<\/jats:bold>\n                    demonstrated higher cytotoxic action than alisertib and GDC\u20100994 against the MCF\u20107 and A549 cancer cell lines. IC\n                    <jats:sub>50<\/jats:sub>\n                    values for these hybrids were 2.59\u2009\u00b1\u20090.13, 4.63\u2009\u00b1\u20090.25, and 5.77\u2009\u00b1\u20090.38, respectively, against MCF\u20107 cell line and were 3.61\u2009\u00b1\u20090.19, 3.85\u2009\u00b1\u20090.21, and 4.23\u2009\u00b1\u20090.15, respectively, against A549. The selected hybrids significantly suppressed p\u2010Aurora A kinase level as well as p\u2010ERK1\/2 level and its upstream regulators p\u2010SRC, p\u2010c\u2010RAF, p\u2010MEK1\/2; meanwhile, ERK downstream effectors FOXO3a level was upregulated, and c\u2010Myc was downregulated, in a dose\u2010dependent manner. The selected hybrids significantly decreased the expression of Bcl\u20102 protein while increasing the levels of\n                    <jats:italic>p53<\/jats:italic>\n                    , caspase\u20107, caspase\u20109, and Bax. They effectively induced pre\u2010G1 phase, G0\/G1 phase apoptosis, and G2\/M phase arrest. The synthesized hybrids possessed favorable binding interactions in the molecular docking investigations as well as appropriate drug\u2010like characteristics.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70364","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:40:07Z","timestamp":1787154007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thiadiazolo\u2010Triazolo\u2010Pyrimidine Hybrids as Dual Aurora A\/ERK Inhibitors: Design, Synthesis, and Apoptotic Activity"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9929-3741","authenticated-orcid":false,"given":"Mai A. 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