Identification of Potent and Selective RORγ Antagonists

Wenwei Huang  1 ,  Hang Wang  1 ,  Ronald L. Johnson  1 ,  Ruili Huang  1 ,  Erika E. Englund  1 ,  Jun Huh  2 ,  Dan R. Littman  2
Affiliations
  • 1. NIH Chemical Genomics Center, NIH Center for Translational Therapeutics,NIH Chemical Genomics Center, National Human Genome Research Institute, NationalInstitutes of Health, Rockville, MD.
  • 2. Skirball Institute of Biomolecular Medicine, New York University, NewYork, NY.
PMID: 23658948
Abstract

Retinoic acid-related Orphan Receptor RORγt plays a pivotal role in the differentiation of Th17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat Th17-related autoimmune diseases. In this report, we present the identification of a series of diphenylpropanamides as novel and selective RORγt antagonists. ML209 inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed Th17 cell differentiation at submicromolar concentrations.