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Dysregulated activity of Syk is implicated in the development of antibody-mediated autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis, but the effect of Syk inhibition on such diseases remains to be fully evaluated. We have developed a novel selective Syk inhibitor, SKI-O-592, and its orally bioavailable salt form, SKI-O-703 (cevidoplenib). To examine the efficacy of SKI-O-703 on the progression of SLE, New Zealand black\/white mice at the autoimmunity-established phase were administrated orally with SKI-O-703 for 16 weeks. Levels of IgG autoantibody, proteinuria, and glomerulonephritis fell significantly, and this was associated with hypoactivation of follicular B cells via the germinal center. In a model of serum-transferred arthritis, SKI-O-703 significantly ameliorated synovitis, with fewer neutrophils and macrophages infiltrated into the synovial tissue. This effect was recapitulated when mice otherwise refractory to anti-TNF therapy were treated by TNF blockade combined with a suboptimal dose of SKI-O-703. These results demonstrate that the novel selective Syk inhibitor SKI-O-703 attenuates the progression of autoantibody-mediated autoimmune diseases by inhibiting both autoantibody-producing and autoantibody-sensing cells.<\/jats:p>","DOI":"10.1093\/cei\/uxac096","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:33:46Z","timestamp":1667910826000},"page":"31-45","source":"Crossref","is-referenced-by-count":13,"title":["A novel selective spleen tyrosine kinase inhibitor SKI-O-703 (cevidoplenib) ameliorates lupus nephritis and serum-induced arthritis in murine models"],"prefix":"10.1093","volume":"211","author":[{"given":"Somi","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University , Seoul 04763 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4394","authenticated-orcid":false,"given":"Eunkyeong","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, College of Medicine, Hanyang University , Seoul 04763 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeyoung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Discovery Biology, Research Institute, Oscotec Inc. , Seongnam-si, Gyeonggi-do 13488 , Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haejun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Discovery Biology, Research Institute, Oscotec Inc. , Seongnam-si, Gyeonggi-do 13488 , 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