RORγt Inverse agonist 10 is a highly potent, orally bioavailable compound that acts as an antagonist for the retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt). With an IC50 of 51 nM, it effectively inhibits RORγt activity, a key transcription factor regulating genes linked to psoriasis pathogenesis, including [IL-17A], [IL-22], and [IL-23R].

RORγt:51 nM (IC50)

RORγt Inverse Agonist 10 exhibits robust stability in liver microsomes, as demonstrated by its clearance rates (human CLint = 0.010 mL/min/mg, mouse CLint = 0.030 mL/min/mg)[1]. Additionally, it effectively inhibits IL-17A production in a dose-dependent manner, achieving an IC50 of 130 nM in human whole-blood assays[1].

RORγt Inverse Agonist 10, administered orally at doses ranging from 3 to 100 mg/kg, significantly suppresses IL-17A production in a dose-dependent manner within a C57/BL6 male mice model employing IL-18/23-induced cytokine expression[1]. Furthermore, an oral dose of 1.145 mg/kg of the same compound has demonstrated a considerable pharmacokinetic profile with an area under the curve (AUC) of 15000 nM*h and a half-life (t 1/2) of 3.6 hours[1]. This study underscores the compound's potential in modulating immune responses through the targeted inhibition of IL-17A production.