{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T23:17:04Z","timestamp":1783552624523,"version":"3.55.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Janus kinase inhibitors have demonstrated efficacy in treating inflammatory and autoimmune diseases; however, several concerns restrict their use in medical practice. One member of this kinase family, tyrosine kinase 2 (TYK2), recently attracted attention owing to the limited number of key inflammatory cytokine pathways it mediates (type I interferon, interleukin [IL]-12\/IL-23, and IL-10 family pathways) and the numerous genetic studies associating polymorphisms of the\n                    <jats:italic>TYK2<\/jats:italic>\n                    gene with protection against several inflammatory and autoimmune diseases. In that regard, we discovered a selective, reversible, ATP-competitive inhibitor of TYK2, GLPG3667. We present the selectivity of GLPG3667 in biochemical, cellular, and human whole blood assays. In vitro, GLPG3667 inhibited the IL-12- and IL-23-induced polarization of T helper (T\n                    <jats:sub>H<\/jats:sub>\n                    )1 and T\n                    <jats:sub>H<\/jats:sub>\n                    17, respectively, but was shown to have a more limited impact on the IL-10 pathway and the anti-inflammatory effects of IL-10 in vitro. Pharmacodynamic analyses performed during phase 1 trials, in which healthy volunteers received GLPG3667 orally, confirmed the selectivity of the compound for TYK2-dependent pathways. In addition, following an in vivo challenge in these healthy volunteers, GLPG3667 inhibited the biological effects of interferon-\u03b1, supporting its potential use in treating several inflammatory and autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1007\/s10753-026-02519-1","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:05:24Z","timestamp":1778911524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Characterization of GLPG3667, a Tyrosine Kinase 2-Selective Inhibitor, for the Treatment of Inflammatory and Autoimmune Diseases"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4883-3154","authenticated-orcid":false,"given":"C\u00e9line","family":"Cottereaux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7533-1778","authenticated-orcid":false,"given":"May-Linda","family":"Lepage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-0544","authenticated-orcid":false,"given":"Isabelle","family":"Parent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-4761","authenticated-orcid":false,"given":"Maikel","family":"Colli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2802-3883","authenticated-orcid":false,"given":"An","family":"Van de Water","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-1238","authenticated-orcid":false,"given":"Emilie","family":"Lagoutte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2618-8697","authenticated-orcid":false,"given":"Christelle","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3881-5832","authenticated-orcid":false,"given":"Maarten","family":"Van Balen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-9660","authenticated-orcid":false,"given":"Adrien","family":"Cosson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-4676","authenticated-orcid":false,"given":"Roland","family":"Blanque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8137-2521","authenticated-orcid":false,"given":"Kenji","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4902-7677","authenticated-orcid":false,"given":"Mia","family":"Jans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0914-926X","authenticated-orcid":false,"given":"Laetitia","family":"Furio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-229X","authenticated-orcid":false,"given":"Steven","family":"Van der Plas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-7124","authenticated-orcid":false,"given":"Reginald","family":"Brys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-1861","authenticated-orcid":false,"given":"David","family":"Amantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4199-9263","authenticated-orcid":false,"given":"Ren\u00e9","family":"Galien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"issue":"7","key":"2519_CR1","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1136\/annrheumdis-2018-214280","volume":"78","author":"KL Winthrop","year":"2019","unstructured":"Winthrop, K.L., M.E. 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Kenji Shoji was an employee of Galapagos SASU at the time of the study and is now an employee of Oncodesign Precision Medicine. Steven Van der Plas was an employee of Galapagos NV at the time of the study and is now an employee of iTeos Therapeutics. Reginald Brys was an employee of Galapagos NV at the time of the study and is now an employee of Agomab Therapeutics. David Amantini was an employee of Galapagos SASU at the time of the study. Ren\u00e9 Galien was an employee of Galapagos SASU at the time of the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"162"}}