The blockade of IL-6 signaling in rational drug design.
After three decades from the development of the hybridoma technology, a monoclonal antibody-based therapy targeting the inflammatory cytokine has been established as an ultimate treatment for chronic inflammatory diseases. Interleukine-6 (IL-6) is one of the inflammatory cytokines playing a pivotal role in these conditions, and strategies targeting IL-6 signal show promise in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, and Crohn's disease. Although many groups have been exploring the approach to block the IL-6 signal, tocilizumab, a humanized monoclonal antibody of the IL-6 receptor, has been the most intensively studied agent for clinical use. Clinical trials regarding chronic inflammatory diseases described above have demonstrated efficacy of tocilizumab, however, this treatment has limitations in terms of economic costs and ease of administration, and further advances are necessary to expand the concept of IL-6-specific therapeutics. In this review, we discuss targeting IL-6 in a rational drug design and present the various strategies to achieve this.
Adachi
Yasuo
Y
Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Yoshio-Hoshino
Naoko
N
Nishimoto
Norihiro
N
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D005871:Castleman Disease / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D015195:Drug Design; D018014:Gene Transfer Techniques; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000276:immunology; D009101:Multiple Myeloma / Q000188:drug therapy; D010455:Peptides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D019947:Receptors, Interleukin-6 / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015850:Interleukin-6; D010455:Peptides; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab