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The signaling pathways associated with IL\u20106 offer promising targets for therapeutic interventions in inflammatory diseases and IL\u20106\u2010dependent tumors. Although certain anti\u2010IL\u20106 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non\u2010peptide molecules acting as IL\u20106 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL\u20106 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure\u2010activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL\u20106 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL\u20106 inhibitors to address the complexities of inflammatory diseases.<\/jats:p>","DOI":"10.1002\/med.22022","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T11:39:24Z","timestamp":1706873964000},"page":"1683-1726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Natural products as IL\u20106 inhibitors for inflammatory diseases: Synthetic and SAR perspective"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-2916","authenticated-orcid":false,"given":"Dipesh S.","family":"Harmalkar","sequence":"first","affiliation":[{"name":"BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy Dongguk 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