Interleukin-17 in disease pathogenesis and therapy: recent advances in targeted drug design and medicinal chemistry

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.