{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:29:08Z","timestamp":1784042948800,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3502801"],"award-info":[{"award-number":["2023YFC3502801"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and tissue damage, driven by dysregulated cytokine signaling and immune cell hyperactivation. Bruton's tyrosine kinase (BTK) mediates pathogenic B\u2010cell activation and autoantibody production, while Janus kinase 3 (JAK3) orchestrates cytokine\u2010driven inflammation through signal transducer and activator of transcription 5 (STAT5) phosphorylation, exacerbating macrophage and monocyte activation. Here, we report Wj1113, a novel dual inhibitor that potently blocks BTK (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a00.7\u00a0nM) and JAK3 (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a026.2\u00a0nM). Wj1113 inhibits B\u2010cell activation via BTK blockade and suppresses JAK3\u2010dependent STAT5 phosphorylation, reducing proinflammatory cytokine secretion and monocyte chemotaxis. In vitro, it suppresses macrophage activation and modulates inflammatory mediator expression. In the collagen\u2010induced arthritis mouse model, Wj1113 treatment dose\u2010dependently reduces joint inflammation, macrophage infiltration, and levels of TNF\u2010\u03b1 (tumor necrosis factor\u2010\u03b1), IL(interleukin)\u20106, anti\u2010cyclic citrullinated peptide antibody (ACPA) and rheumatoid factor (RF), while elevating anti\u2010inflammatory IL\u201010. Histopathological and micro\u2010CT analyses confirm attenuation of cartilage\/bone erosion and synovial hyperplasia. Mechanistically, Wj1113 inhibits BTK\/JAK3 signaling in vivo and alleviates arthritis in joints. Collectively, these findings establish Wj1113 as a promising dual\u2010target therapeutic candidate for RA, addressing both B\u2010cell and cytokine\u2010driven pathogenic pathways.<\/jats:p>","DOI":"10.1002\/mco2.70207","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:21:24Z","timestamp":1751876484000},"source":"Crossref","is-referenced-by-count":5,"title":["A Novel Dual Bruton's Tyrosine Kinase\/Janus Kinase 3 Inhibitor Wj1113 and its Therapeutic Effects on Rheumatoid Arthritis"],"prefix":"10.1002","volume":"6","author":[{"given":"Chunyu","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-6208","authenticated-orcid":false,"given":"Fangfang","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University) Ministry of Education Yantai University Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyi","family":"Que","sequence":"additional","affiliation":[{"name":"Department of Oncology The Second Hospital of Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Xue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taigang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Medicinal Basic Research Innovation Center of Chronic Kidney Disease Ministry of Education Shanxi Medical University Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2015.04.009"},{"issue":"10","key":"e_1_2_9_3_1","first-page":"591","article-title":"Global Epidemiology of Rheumatoid Arthritis","volume":"18","author":"Finckh 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