Biaryl amides as new RORγt modulators were discovered. The crystal structure of biaryl amide agonist in complex with RORγt ligand binding domain (LBD) was resolved, and both "short" and "long" inverse agonists were obtained by removing from or adding to a proper structural moiety. While "short" inverse agonist () recruits a corepressor peptide and dispels a coactivator peptide, "long" inverse agonist () dispels both. The two types of inverse agonists can be utilized as potential tools to study mechanisms of Th17 transcriptional network inhibition and related disease biology.
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| http://dx.doi.org/10.1021/acsmedchemlett.7b00476 | DOI Listing |
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