{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:03:30Z","timestamp":1784887410220,"version":"3.55.0"},"reference-count":137,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Interleukin-17 (IL-17) is a key pro-inflammatory cytokine that plays an essential role in host defense and immune regulation. Dysregulated IL-17 expression and signaling are implicated in the pathogenesis of a broad range of chronic inflammatory and autoimmune diseases, including psoriasis, systemic lupus erythematosus, periodontitis, and cancer. Increasing insights into IL-17 receptor engagement and downstream signaling networks, have established the IL-17 axis as a promising therapeutic target. Monoclonal antibodies targeting IL-17 or its receptor have demonstrated substantial clinical efficacy; however, their widespread application is limited by high cost, suboptimal tissue penetration, potential immunogenicity, and therapy-associated adverse effects. These limitations have driven growing interest in the development of alternative therapeutic strategies. This review provides a comprehensive overview of IL-17 signaling pathways and their contributions to disease pathogenesis and systematically summarizes current therapeutic approaches targeting the IL-17 axis, including monoclonal antibodies and emerging small-molecule inhibitors. Collectively, these insights offer a conceptual framework to support the rational design and development of next-generation IL-17-targeted therapeutics.<\/jats:p>","DOI":"10.3389\/fphar.2026.1836187","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:46:26Z","timestamp":1784090786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-17 in disease pathogenesis and therapy: recent advances in targeted drug design and medicinal chemistry"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Cariology and Endodontics, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nursing, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontics, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxin","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of West Outpatient, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1021\/acsmedchemlett.2c00257","article-title":"Multicomponent macrocyclic IL-17a modifier","volume":"13","author":"Abdelraheem","year":"2022","journal-title":"ACS Med. 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