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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 4n inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human T_H17 cell differentiation at sub-micromolar concentrations.

SUBMITTER: Huh JR

PROVIDER: S-EPMC3770298 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors.

Huh Jun R JR Englund Erika E EE Wang Hang H Huang Ruili R Huang Pengxiang P Rastinejad Fraydoon F Inglese James J Austin Christopher P CP Johnson Ronald L RL Huang Wenwei W Littman Dan R DR

ACS medicinal chemistry letters 20130101 1

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 cel ...[more]

PMID: 24040486

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