RT Journal Article
SR Electronic
T1 Increasing Human Th17 Differentiation through Activation of Orphan Nuclear Receptor Retinoid Acid-Related Orphan Receptor γ (RORγ) by a Class of Aryl Amide Compounds
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 583
OP 590
DO 10.1124/mol.112.078667
VO 82
IS 4
A1 Wei Zhang
A1 Jing Zhang
A1 Leiping Fang
A1 Ling Zhou
A1 Shuai Wang
A1 Zhijun Xiang
A1 Yuan Li
A1 Bruce Wisely
A1 Guifeng Zhang
A1 Gang An
A1 Yonghui Wang
A1 Stewart Leung
A1 Zhong Zhong
YR 2012
UL http://molpharm.aspetjournals.org/content/82/4/583.abstract
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.