Identification of Potent and Selective Diphenylpropanamide ROR纬 Inhibitors

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• 作者：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. Littman
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：January 10, 2013
• 年：2013
• 卷：4
• 期：1
• 页码：79-84
• 全文大小：424K
• 年卷期：v.4,no.1(January 10, 2013)
• ISSN：1948-5875

文摘

Retinoic acid-related orphan receptor ROR纬t plays a pivotal role in the differentiation of T_H17 cells. Antagonizing ROR纬t 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 ROR纬 antagonists. Diphenylpropanamide 4n inhibited the transcriptional activity of ROR纬t, but not ROR伪, in cells. In addition, it suppressed human T_H17 cell differentiation at submicromolar concentrations.

Keywords:

retinoic acid-related orphan receptor; ROR纬 antagonist; diphenylpropanamide; T_H17-related autoimmune diseases