TY - JOUR
T1 - Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking
AU - Nada, Hossam
AU - Sivaraman, Aneesh
AU - Lu, Qili
AU - Min, Kyoungho
AU - Kim, Sungdo
AU - Goo, Ja Il
AU - Choi, Yongseok
AU - Lee, Kyeong
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/4/13
Y1 - 2023/4/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151361439&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.2c01957
DO - 10.1021/acs.jmedchem.2c01957
M3 - Review article
C2 - 36971365
AN - SCOPUS:85151361439
SN - 0022-2623
VL - 66
SP - 4417
EP - 4433
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -