强效和选择性二苯基丙酰胺RORγ抑制剂的鉴定
Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors.
作者信息
Huh Jun R, Englund Erika E, Wang Hang, Huang Ruili, Huang Pengxiang, Rastinejad Fraydoon, Inglese James, Austin Christopher P, Johnson Ronald L, Huang Wenwei, Littman Dan R
机构信息
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.
出版信息
ACS Med Chem Lett. 2013 Jan 10;4(1):79-84. doi: 10.1021/ml300286h.
Abstract
Retinoic acid-related orphan receptor RORγt plays a pivotal role in the differentiation of T17 cells. Antagonizing RORγt transcriptional activity is a potential means to treat T17-related autoimmune diseases. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective RORγ antagonists. Diphenylpropanamide inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed human T17 cell differentiation at sub-micromolar concentrations.
摘要
维甲酸相关孤儿受体RORγt在T17细胞分化中起关键作用。拮抗RORγt转录活性是治疗T17相关自身免疫性疾病的一种潜在手段。在此，我们描述了一系列二苯基丙酰胺作为新型选择性RORγ拮抗剂的鉴定。二苯基丙酰胺在细胞中抑制RORγt的转录活性，但不抑制RORα。此外，它在亚微摩尔浓度下抑制人T17细胞分化。
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