RORγt agonist 8-074 is a potent, selective RORγt agonist with Kd of 497 nM, shows potent RORγt agonist activity in the Gal4 reporter gene assay with EC50 of 118.7 nM, and EC50 of 19.95 nM in FRET assays.
RORγt agonist 8-074 displayed high selectivity versus the other two ROR members.
RORγt agonist 8-074 demonstrates stimulating the mouse Tc17 cells with EC50 at 11.21 nM.
RORγt agonist 8-074 demonstrated potent and selective binding to the RORγt protein as well as potent in vitro activity compared with LYC-55716.
RORγt agonist 8-074 promoted the secretion of IL-17A by Th17 cells with EC50 of 22.78 nM.
RORγt agonist 8-074 (160 nM) significantly increased the percentage of CD4+ T and CD8+ T cells that express IL-17A (from 12.1% to 24.0% in CD4+ T and 22.9% to 50.4% in CD8+ T cells).
RORγt agonist 8-074 (50 mg/kg, i.p. injection, QD over two weeks) showed robust antitumor efficacy in syngeneic tumor models, and 8-074 improved the efficacy of anti‑PD‑1 therapy in murine lung cancer models.