{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:50:49Z","timestamp":1792000249929,"version":"4.4.0"},"reference-count":79,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Janus kinase (Jak)\/signal transducer and activating protein (STAT) pathways mediate the intracellular signaling of cytokines in a wide spectrum of cellular processes. They participate in physiologic and inflammatory cascades and have become a major focus of research, yielding novel therapies for immune-mediated inflammatory diseases (IMID). Genetic linkage has related dysfunction of Tyrosine kinase 2 (Tyk2)\u2014the first member of the Jak family that was described\u2014to protection from psoriasis. Furthermore, Tyk2 dysfunction has been related to IMID prevention, without increasing the risk of serious infections; thus, Tyk2 inhibition has been established as a promising therapeutic target, with multiple Tyk2 inhibitors under development. Most of them are orthosteric inhibitors, impeding adenosine triphosphate (ATP) binding to the JH1 catalytic domain\u2014which is highly conserved across tyrosine kinases\u2014and are not completely selective. Deucravacitinib is an allosteric inhibitor that binds to the pseudokinase JH2 (regulatory) domain of Tyk2; this unique mechanism determines greater selectivity and a reduced risk of adverse events. In September 2022, deucravacitinib became the first Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis. A bright future can be expected for Tyk2 inhibitors, with newer drugs and more indications to come.<\/jats:p>","DOI":"10.3390\/ijms24043391","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T01:59:43Z","timestamp":1675907983000},"page":"3391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Tyk2 Targeting in Immune-Mediated Inflammatory Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3421-7756","authenticated-orcid":false,"given":"Llu\u00eds","family":"Rusi\u00f1ol","sequence":"first","affiliation":[{"name":"Department of Dermatology IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-0952","authenticated-orcid":false,"given":"Luis","family":"Puig","sequence":"additional","affiliation":[{"name":"Department of Dermatology IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ad.2020.12.003","article-title":"Janus Kinase Inhibitors in Dermatology: Part 1\u2014General Considerations and Applications in Vitiligo and Alopecia Areata","volume":"112","author":"Puig","year":"2021","journal-title":"Actas Dermo-Sifiliogr\u00e1ficas Engl. 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