TY - JOUR T1 - Increasing Human Th17 Differentiation Through Activation of Orphan Nuclear Receptor RORγ by a Class of Aryl Amide Compounds JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.078667 SP - mol.112.078667 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 Y1 - 2012/06/14 UR - http://molpharm.aspetjournals.org/content/early/2012/06/14/mol.112.078667.abstract N2 - In a screen for small molecule inhibitors of RORγ, we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the 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 ~0.1μgM 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. ER -