1854901-94-2

TAK-828F is a potent and selective orally available RORγt inverse agonist. TAK-828F showed Binding IC50 = 1.9 nM; Reporter gene IC50=6.1 nM; logD=3.53; LLE (reporter gene)=4.68. TAK-828F inhibited IL-17 production from mouse splenocytes and human peripheral blood mononuclear cells dose-dependently at concentrations of 0.01-10?μM without affecting the production of IFN-γ. TAK-828F may provide a novel therapeutic option to treat immune diseases by inhibiting Th17 and Th1/17 cells' differentiation and improving imbalance between Th17 and Treg cells.

TAK-828F is a potent, selective, and orally available retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonist (binding IC50=1.9 nM, reporter gene IC50=6.1 nM). TAK-828F shows excellent RORγt isoforms selectivity (>5000-fold selectivity against human RORα and RORβ)[1].

[1] Kono M, et al. Discovery of [ cis-3-({(5 R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1 H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5 H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Reti DOI:10.1021/acs.jmedchem.8b00061