title: Inhibiting RORγt/Th17 axis for autoimmune disorders.
abstract: The recent success reported in late-stage clinical trials for the treatment of psoriasis by antibodies directed against interleukin (IL)-17 or its receptor has validated and strongly supports the development of inhibitors of the IL-17 pathway as a new therapeutic modality in chronic inflammation and autoimmunity. These results also encourage the drug discovery of orally available small molecules that can modulate down the production of IL-17 by Th17 cells (the major IL-17 producers) or the downstream signaling of the IL-17 receptor. Here, we review these strategies with an emphasis on inhibiting the retinoic-acid-related orphan nuclear receptor RORγt, which is the master regulator of Th17 cells and a promising therapeutic target for the treatment of multiple autoimmune disorders.
authors.affiliation: Frontier Research Laboratories, Daiichi Sankyo Co., Shinagawa-ku, Tokyo 140-3710, Japan. Electronic address: isono.fujio.vd@daiichisankyo.co.jp.
authors.forename: Fujio
authors.initials: F
authors.lastname: Isono
authors.affiliation: Oncology Research Laboratories, Daiichi Sankyo Co., Shinagawa-ku, Tokyo 140-3710, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fujita-Sato
authors.affiliation: Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Edogawa-ku, Tokyo 134-8630, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use*; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054852:Small Molecule Libraries