Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 66, Issue 7, Pages 4417-4433Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.2c01957
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Interleukin-6 (IL-6) is a significant factor in inflammatory and autoimmune diseases, and its targeted therapy is promising but still faces challenges. This study focuses on the development of small molecule inhibitors for IL-6 through analysis of protein-protein inhibitors targeting the IL-6/IL-6 receptor/gp130 complex.
Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a key role in the pathogenesis and physiology of inflammatory and autoimmune diseases, such as coronary heart disease, cancer, Alzheimer's disease, asthma, rheumatoid arthritis, and most recently COVID-19. IL-6 and its signaling pathway are promising targets in the treatment of inflammatory and autoimmune diseases. Although, anti-IL-6 monoclonal antibodies are currently being used in clinics, huge unmet medical needs remain because of the high cost, administration-related toxicity, lack of opportunity for oral dosing, and potential immunogenicity of monoclonal antibody therapy. Furthermore, nonresponse or loss of response to monoclonal antibody therapy has been reported, which increases the importance of optimizing drug therapy with small molecule drugs. This work aims to provide a perspective for the discovery of novel small molecule IL-6 inhibitors by the analysis of the structure-activity relationships and computational studies for protein-protein inhibitors targeting the IL-6/IL-6 receptor/gp130 complex.
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