Biaryl amides as new RORγt modulators were discovered. The crystal structure of biaryl amide agonist 6 in complex with RORγt ligand binding domain (LBD) was resolved, and both “short” and “long” inverse agonists were obtained by removing from 6 or adding to 6 a proper structural moiety. While “short” inverse agonist (8) recruits a corepressor peptide and dispels a coactivator peptide, “long” inverse agonist (9) 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.

中文翻译：

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从RORγt激动剂到两种RORγt逆激动剂

发现了作为新的RORγt调节剂的联芳基酰胺。联芳基酰胺激动剂的晶体结构6在配合物与RORγt配体结合域（LBD）得到了解决，并且两个“短”和“长”逆通过从除去得到激动剂6或添加到6的适当结构部分。“短”反向激动剂（8）募集了一个corepressor肽并消除了共激活肽，而“长”反向激动剂（9）则消除了两者。两种类型的反向激动剂可以用作研究Th17转录网络抑制机制和相关疾病生物学的潜在工具。