Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors

Abstract

Retinoic acid-related orphan receptor RORγt plays a pivotal role in the differentiation of T_H17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat T_H17-related autoimmune diseases. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective RORγ antagonists. Diphenylpropanamide <b>4n</b> inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human T_H17 cell differentiation at sub-micromolar concentrations.