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This study aims to explore the effects of YC\u20104\u20103, the patented chemical synthesis of benzothiazepinone compounds (BTZs), a novel GSK\u20103\u03b2 inhibitor (GSK\u20103\u03b2i), on macrophages in ITP. The expressions of GSK\u20103\u03b2 in monocytes are tested. The effects of GSK\u20103\u03b2i (YC\u20104\u20103) on macrophages of ITP patients are examined and validated in passive and active murine models. Signal pathway enrichment analysis is performed. The interaction proteins of endoplasmic reticulum (ER) stress and GSK\u20103\u03b2 are explored. The GSK\u20103\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    cells in monocytes are increased in newly diagnosed ITP patients and decreased in treatment\u2010response patients. YC\u20104\u20103 can restrain the proinflammatory differentiation, phagocytosis, and cytokine generation of macrophages and alleviate thrombocytopenia in ITP. YC\u20104\u20103 suppresses the PI3K\/mTOR\/Akt, NF\u03baB\/I\u03baB\u03b1, and MAPK pathways, as well as the ER stress signal pathway. YC\u20104\u20103 directly interacts with the protein chaperone Bip. YC\u20104\u20103, a patented GSK\u20103\u03b2i, can modulate the inflammatory status of macrophages and improve the thrombocytopenia in ITP by directly interacting with ER stress response. YC\u20104\u20103 may be a novel potential therapeutic agent for ITP.\n                  <\/jats:p>","DOI":"10.1002\/advs.202412515","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:28:50Z","timestamp":1741739330000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["YC\u20104\u20103, a Novel Glycogen Synthase Kinase 3\u03b2 Inhibitor, Alleviates the Endoplasmic Reticulum Stress of Macrophages in Primary Immune Thrombocytopenia"],"prefix":"10.1002","volume":"12","author":[{"given":"Pengcheng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology Zhongshan Hospital Fudan University  Shanghai 200032 China"},{"name":"Department of Hematology Zhongshan Hospital Qingpu Branch Fudan University  Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ji","sequence":"additional","affiliation":[{"name":"Department 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