GSK805

GSK805 is a potent, orally bioavailable retinoid-related orphan receptor gamma t (RORγt) inverse agonist that interacts with the receptors putative ligand binding domain without exerting significant effects on DNA binding. It inhibits the expression of IL-17 (at 0.5 µM) in naïve CD4+ T cells activated under Th17-cell-polarizing conditions and affects the broader RORγt-dependent gene network, inhibiting the development and pathogenic function of Th17 cells. GSK805 significantly reduces the severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, when given...