Description: TAK-828F (TAK828F) is a novel, potent, selective, and orally bioavailable retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonist with binding IC50 of 1.9 nM and reporter gene IC50 of 6.1 nM. TAK-828F shows excellent RORγt isoforms selectivity (>5000-fold selectivity against human RORα and RORβ). TAK-828F showed potent RORγt inverse agonistic activity, excellent selectivity against other ROR isoforms and nuclear receptors, and a good pharmacokinetic profile. In animal studies, oral administration of compound 10 exhibited robust and dose-dependent inhibition of IL-17A cytokine expression in a mouse IL23-induced gene expression assay. Furthermore, development of clinical symptoms in a mouse experimental autoimmune encephalomyelitis model was significantly reduced. Compound 10 was selected as a clinical compound for the treatment of Th17-driven autoimmune diseases.