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Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors
journal contribution
posted on 2013-01-10, 00:00 authored by Jun R. Huh, Erika
E. Englund, Hang Wang, Ruili Huang, Pengxiang Huang, Fraydoon Rastinejad, James Inglese, Christopher P. Austin, Ronald L. Johnson, Wenwei Huang, Dan R. LittmanRetinoic 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
the transcriptional activity of RORγt, but not RORα, in
cells. In addition, it suppressed human TH17 cell differentiation
at submicromolar concentrations.