Inhibiting RORγt/Th17 axis for autoimmune disorders

Drug Discovery Today - Tập 19 - Trang 1205-1211 - 2014
Fujio Isono1, Saori Fujita-Sato2, Shuichiro Ito3
1Frontier Research Laboratories, Daiichi Sankyo Co., Shinagawa-ku, Tokyo 140-3710, Japan
2Oncology Research Laboratories, Daiichi Sankyo Co., Shinagawa-ku, Tokyo 140-3710, Japan
3Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Edogawa-ku, Tokyo 134-8630, Japan

Tài liệu tham khảo

Lin, 2008, TNFα blockade in human diseases: an overview of efficacy and safety, Clin. Immunol., 126, 13, 10.1016/j.clim.2007.08.012 Bell, 2011, Biologic therapies in non-rheumatic diseases: lessons for rheumatologists?, Nat. Rev. Rheumatol., 7, 507, 10.1038/nrrheum.2011.106 Kolls, 2004, Interleukin-17 family members and inflammation, Immunity, 21, 467, 10.1016/j.immuni.2004.08.018 Miossec, 2009, Interleukin-17 and Type 17 helper T cells, N. Engl. J. Med., 361, 888, 10.1056/NEJMra0707449 Leonardi, 2012, Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis, N. Engl. J. Med., 366, 1190, 10.1056/NEJMoa1109997 Papp, 2012, Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis, N. Engl. J. Med., 366, 1181, 10.1056/NEJMoa1109017 Eberl, 2003, The role of the nuclear hormone receptor RORγt in the development of lymph nodes and Peyer's patches, Immunol. Rev., 195, 81, 10.1034/j.1600-065X.2003.00074.x Huh, 2012, Small molecule inhibitors of RORγt: targeting Th17 cells and other applications, Eur. J. Immunol., 42, 2232, 10.1002/eji.201242740 Miossec, 2012, Targeting IL-17 and TH17 cells in chronic inflammation, Nat. Rev. Drug Discov., 11, 763, 10.1038/nrd3794 Weaver, 2013, The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin, Ann. Rev. Pathol. Mech. Dis., 8, 477, 10.1146/annurev-pathol-011110-130318 Pöllinger, 2012, IL-17 producing T cells in mouse models of multiple sclerosis and rheumatoid arthritis, J. Mol. Med., 90, 613, 10.1007/s00109-011-0841-4 Cua, 2003, Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain, Nature, 421, 744, 10.1038/nature01355 Murphy, 2003, Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation, J. Exp. Med., 198, 1951, 10.1084/jem.20030896 Yen, 2006, IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6, J. Clin. Invest., 116, 1310, 10.1172/JCI21404 Knight, 2013, Genomic modulators of the immune response, Trends Genet., 29, 74, 10.1016/j.tig.2012.10.006 Ivanov, 2006, The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells, Cell, 126, 1121, 10.1016/j.cell.2006.07.035 Annunziato, 2007, Phenotype and functional features of human Th17 cells, J. Exp. Med., 204, 1849, 10.1084/jem.20070663 Solt, 2012, Action of RORs and their ligands in (patho)physiology, Trends Endocrinol. Metab., 23, 619, 10.1016/j.tem.2012.05.012 Eberl, 2004, An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells, Nat. Immunol., 5, 64, 10.1038/ni1022 Sun, 2000, Requirement for RORgamma in thymocyte survival and lymphoid organ development, Science, 288, 2369, 10.1126/science.288.5475.2369 Yang, 2008, Molecular antagonism and plasticity of regulatory and inflammatory T cell programs, Immunity, 29, 44, 10.1016/j.immuni.2008.05.007 Wang, 2010, A second class of nuclear receptors for oxysterols: regulation of RORα and RORγ activity by 24S-hydroxycholesterol (cerebrosterol), Biochim. Biophys. Acta, 1801, 917, 10.1016/j.bbalip.2010.02.012 Wang, 2010, Modulation of retinoic acid receptor-related orphan receptor α and γ activity by 7-oxygenated sterol ligands, J. Biol. Chem., 285, 5013, 10.1074/jbc.M109.080614 Kumar, 2010, The benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-{4-{2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl}phenyl}-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-α/γ inverse agonist, Mol. Pharmacol., 77, 228, 10.1124/mol.109.060905 Huh, 2011, Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity, Nature, 472, 486, 10.1038/nature09978 Fujita-Sato, 2011, Structural basis of digoxin that antagonizes RORγt receptor activity and suppress Th17 cell differentiation and interleukin-17 production, J. Biol. Chem., 286, 31409, 10.1074/jbc.M111.254003 Xu, 2011, Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORγt protein, J. Biol. Chem., 286, 22707, 10.1074/jbc.C111.250407 de Lera, 2007, Design of selective nuclear receptor modulators: RAR and RXR as a case study, Nat. Rev. Drug Discov., 6, 811, 10.1038/nrd2398 Jin, 2010, Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma, Mol. Endocrinol., 24, 923, 10.1210/me.2009-0507 Hann, 2012, Finding the sweet spot: the role of nature and nurture in medicinal chemistry, Nat. Rev. Drug Discov., 11, 355, 10.1038/nrd3701 Solt, 2011, Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand, Nature, 472, 491, 10.1038/nature10075 Kumar, 2012, Identification of SR 2211, a potent synthetic RORγ-selective modulator, ACS Chem. Biol., 7, 672, 10.1021/cb200496y Solt, 2012, Identification of a selective RORγ ligand that suppresses TH17 cells and stimulates T regulatory cells, ACS Chem. Biol., 7, 1515, 10.1021/cb3002649 Khan, 2013, Small molecule amides as potent ROR-γ selective modulators, Bioorg. Med. Chem. Lett., 23, 532, 10.1016/j.bmcl.2012.11.025 Huh, 2013, Identification of potent and selective diphenylpropanamide RORγ inhibitors, ACS Med. Chem. Lett., 4, 79, 10.1021/ml300286h Meissburger, 2011, Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma, EMBO Mol. Med., 3, 637, 10.1002/emmm.201100172 Steinman, 2010, Mixed results with modulation of TH-17 cells in human autoimmune diseases, Nat. Immunol., 11, 41, 10.1038/ni.1803 Blumberg, 2012, Unraveling the autoimmune translational research process layer by layer, Nat. Med., 18, 35, 10.1038/nm.2632 Steinman, 2012, Optimization of current and future therapy for autoimmune diseases, Nat. Med., 18, 59, 10.1038/nm.2625 Cotsapas, 2013, Immune-mediated disease genetics: the shared basis of pathogenesis, Trends Immunol., 34, 22, 10.1016/j.it.2012.09.001 Rutz, 2013, IL-22, not simply a Th17 cytokine, Immnol. Rev., 252, 116, 10.1111/imr.12027 Pantelyushin, 2012, RORγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice, J. Clin. Invest., 122, 2252, 10.1172/JCI61862 Ciofani, 2012, A validated regulatory network for Th17 cell specification, Cell, 151, 289, 10.1016/j.cell.2012.09.016 Wang, 2013, The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90, Nat. Immunol., 14, 72, 10.1038/ni.2479 Garg, 2013, The deubiquitinase A20 mediates feedback inhibition of interleukin-17 receptor signaling, Sci. Signal., 6, ra44, 10.1126/scisignal.2003699 Ma, 2012, A20: linking a complex regulator of ubiquitylation to immunity and human disease, Nat. Rev. Immunol., 12, 774, 10.1038/nri3313 Robinson, 2013, Mechanistic biomarkers for clinical decision making in rheumatic diseases, Nat. Rev. Rheumatol., 9, 267, 10.1038/nrrheum.2013.14