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The OSe\u2010based thiazol <jats:bold>9<\/jats:bold> showed the highest growth inhibition % (GI%) of 64.72% relative to the positive reference doxorubicin (DOX), with a GI% of 79.5%. Furthermore, the novel OSe derivatives showed low GI% values compared to the normal cell lines employed, demonstrating their selectivity. The OSe tethered <jats:italic>N<\/jats:italic>\u2010chloroacetamide <jats:bold>5<\/jats:bold> and Schiff base <jats:bold>19<\/jats:bold> showed a cytotoxic effect with an IC<jats:sub>50<\/jats:sub> of (25.07 and 11.61\u2009\u00b5M), respectively, against the A549 tumor cell line and IC<jats:sub>50<\/jats:sub> of (34.22 and 20.12\u2009\u00b5M), respectively, against the HELA cancer cell line. Enzyme\u2010linked immunosorbent assay to study the JAK1 and the STAT3 inhibitory potentials of OSe compounds <jats:bold>5<\/jats:bold> and <jats:bold>19<\/jats:bold> in the A549 cancer cells both showed promising inhibitory activities with IC<jats:sub>50<\/jats:sub> values of 25.07 and 11.61\u2009\u00b5M, respectively. Protein expression analysis on the A549 cancer cell line on OSe compounds <jats:bold>5<\/jats:bold> and <jats:bold>19<\/jats:bold> showed upregulation of P53, BAX, and Caspases 3, 6, 8, and 9 as apoptotic proteins. However, both candidates expressed downregulation of the antiapoptotic proteins (BCL2, MMP2, and MMP9). Moreover, OSe compounds <jats:bold>5<\/jats:bold> and <jats:bold>19<\/jats:bold> described the downregulation of the examined inflammatory proteins: COX2, IL\u20106, and IL\u20101\u03b2. In addition, OSe compound <jats:bold>19<\/jats:bold> showed potential cell cycle arrest at the G0, S, and G2\u2010M layers, with an increase in cellular levels. Finally, molecular docking studies of OSe compound <jats:bold>19<\/jats:bold> showed the most promising inhibitory potential toward the JAK1 and STAT3 target receptors, with binding scores and interactions exceeding that of the cocrystallized inhibitor of JAK1.<\/jats:p>","DOI":"10.1002\/ddr.70075","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T02:35:16Z","timestamp":1742351716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Innovative Multitarget Organoselenium Hybrids With Apoptotic and Anti\u2010Inflammatory Properties Acting as JAK1\/STAT3 Suppressors"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-6260","authenticated-orcid":false,"given":"Saad","family":"Shaaban","sequence":"first","affiliation":[{"name":"Department of Chemistry College of Science, King Faisal University Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya Yaseen Mahmood","family":"Alabdali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy The University of Mashreq Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai H. 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