Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking

Hossam Nada, Aneesh Sivaraman, Qili Lu, Kyoungho Min, Sungdo Kim, Ja Il Goo, Yongseok Choi, Kyeong Lee

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4417-4433
Number of pages17
JournalJournal of Medicinal Chemistry
Volume66
Issue number7
DOIs
Publication statusPublished - 2023 Apr 13

Bibliographical note

Funding Information:
This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [No. 2018R1A5A2023127 and No. 2023R1A2C3004599]. This work is also supported by the BK21 FOUR program, which was funded by the Ministry of Education of Korea through NRF.

Publisher Copyright:
© 2023 American Chemical Society.

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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