Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking
  • Nada, Hossam
  • Sivaraman, Aneesh
  • Lu, Qili
  • Min, Kyoungho
  • Kim, Sungdo
  • ... Lee, Kyeong
  • 외 2명
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초록

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.

키워드

Antibodies, MonoclonalInterleukin-6Interleukin-6 InhibitorsAntiasthmatic AgentAntineoplastic AgentAntirheumatic AgentCorticosteroidCytokine Receptor AntagonistGlycoprotein Gp 130Interleukin 6Interleukin 6 ReceptorMonoclonal AntibodyAsthmaCalculationCarcinogenesisCoronavirus Disease 2019Drug ApprovalDrug DesignGiant Cell ArteritisHumanIl 6 SignalingIschemic Heart DiseaseMalignant NeoplasmMolecular DockingMyelooptic NeuropathyNonhumanPathogenesisProtein TargetingReviewRheumatoid ArthritisStructure Activity RelationAutoimmune DiseaseAntibodies, MonoclonalAutoimmune DiseasesCovid-19HumansInterleukin-6Interleukin-6 InhibitorsMolecular Docking SimulationStructure-activity RelationshipGIANT-CELL ARTERITISTHERAPEUTIC MONOCLONAL-ANTIBODIESGROWTH-FACTORINTERLEUKIN-6 IL-6SIGNALING PATHWAYCRYSTAL-STRUCTUREAORTIC-ANEURYSMMADINDOLINE-ACANCERRECEPTOR
제목
Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking
저자
Nada, HossamSivaraman, AneeshLu, QiliMin, KyounghoKim, SungdoGoo, Ja-IlChoi, YongseokLee, Kyeong
DOI
10.1021/acs.jmedchem.2c01957
발행일
2023-04
유형
Article
저널명
Journal of Medicinal Chemistry
66
7
페이지
4417 ~ 4433