PT  - JOURNAL ARTICLE
AU  - Wei Zhang
AU  - Jing Zhang
AU  - Leiping Fang
AU  - Ling Zhou
AU  - Shuai Wang
AU  - Zhijun Xiang
AU  - Yuan Li
AU  - Bruce Wisely
AU  - Guifeng Zhang
AU  - Gang An
AU  - Yonghui Wang
AU  - Stewart Leung
AU  - Zhong Zhong
TI  - Increasing Human Th17 Differentiation through Activation of Orphan Nuclear Receptor Retinoid Acid-Related Orphan Receptor γ (RORγ) by a Class of Aryl Amide Compounds
AID  - 10.1124/mol.112.078667
DP  - 2012 Oct 01
TA  - Molecular Pharmacology
PG  - 583--590
VI  - 82
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/82/4/583.short
4100  - http://molpharm.aspetjournals.org/content/82/4/583.full
SO  - Mol Pharmacol2012 Oct 01; 82
AB  - In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC50. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.