Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors

  • ACS Med Chem Lett. 2013 Jan 10;4(1):79-84. doi: 10.1021/ml300286h.
Jun R Huh  1 ,  Erika E Englund ,  Hang Wang ,  Ruili Huang ,  Pengxiang Huang ,  Fraydoon Rastinejad ,  James Inglese ,  Christopher P Austin ,  Ronald L Johnson ,  Wenwei Huang ,  Dan R Littman
Affiliations
  • 1. Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
PMID: 24040486 DOI: 10.1021/ml300286h
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. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective RORγ antagonists. Diphenylpropanamide 4n inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human TH17 cell differentiation at sub-micromolar concentrations.

Keywords
RORγ antagonist; Retinoic acid-related orphan receptor; TH17-related autoimmune diseases; diphenylpropanamide.
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