GSK805

GSK805 is a potent, CNS-penetrant, orally bioavailable small molecule inverse agonist of retinoid-related orphan receptor gamma t (RORγt)[1][5][13]. It inhibits the differentiation and function of T helper 17 (Th17) cells by modulating RORγt-dependent transcription. GSK805 reduces IL-17 production and decreases inflammatory cytokines (IL-23R, TNF-α, IFN-γ) in cellular and mouse models of autoimmune disease such as experimental autoimmune encephalomyelitis (EAE, a murine model of multiple sclerosis) and cholestatic liver diseases (primary biliary cholangitis and primary sclerosing cholangitis)[2][5]. It achieves high liver concentrations, modulates inflammation, and does not significantly impair general well-being in mouse models[2]. Its mechanism involves binding the RORγt ligand-binding domain inhibiting downstream transcription without disrupting DNA binding[5][3]. It is used in research settings for immune modulation and investigation of Th17-driven diseases.

Other names

N-(2,6-dichloro-2'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide