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[摘要]：Nuclear receptors (NRs) are ligand-regulated transcription factors that display canonical domain structure with highly conserved DNA binding and ligand binding domains. The identification of the endogenous ligands for several receptors remains elusive or is controversial, and thus these receptors are classified as orphans. One such orphan receptor is the retinoic acid receptor-related orphan receptor gamma (ROR gamma). An isoform of ROR gamma, ROR gamma t, has been shown to be essential for the expression of Interleukin 17 (IL-17) and the differentiation of Th17 cells. 1117 cells have been implicated in the pathology of several autoimmune diseases, including multiple sclerosis, (MS) and rheumatoid arthritis (RA). Genetic ablation of ROR gamma alone or in combination with ROR alpha in mice led to impaired Th17 differentiation and protected the mice from development of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, Here we describe SR2211, a selective ROR gamma modulator that potently inhibits production of IL-17 in cells. |
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