强效和选择性RORγ拮抗剂的鉴定
Identification of Potent and Selective RORγ Antagonists
作者信息
Huang Wenwei, Wang Hang, Johnson Ronald L., Huang Ruili, Englund Erika E., Huh Jun, Littman Dan R.
机构信息
NIH Chemical Genomics Center, NIH Center for Translational Therapeutics, NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Rockville, MD.
Skirball Institute of Biomolecular Medicine, New York University, New York, NY.
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. In this report, we present the identification of a series of diphenylpropanamides as novel and selective RORγt antagonists. ML209 inhibited transcriptional activity of RORγt, but not RORα, in cells. In addition, it suppressed Th17 cell differentiation at submicromolar concentrations.
维甲酸相关孤儿受体RORγt在Th17细胞分化中起关键作用。拮抗RORγt转录活性是治疗Th17相关自身免疫性疾病的一种潜在手段。在本报告中，我们介绍了一系列二苯基丙酰胺作为新型选择性RORγt拮抗剂的鉴定结果。ML209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可抑制Th17细胞分化。
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