From RORγt Agonist to Two Types of RORγt Inverse Agonists
| Autor: | Xiaoxia Song, Feng Ren, Qian Liu, Yafei Huang, Wei Cai, Zhijun Xiang, Jia-Ning Xiang, Tang Ting, Qianqian Wu, Yingli Ma, Xichen Lin, Mercedes Lobera, Guifeng Zhang, Ling Zhou, Liming Shao, Ting Yang, Stewart Leung, Liuqing Yang, Wang Yonghui, Lisa A. Orband-Miller |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Agonist Stereochemistry medicine.drug_class Organic Chemistry Peptide Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry RAR-related orphan receptor gamma Amide Drug Discovery Coactivator medicine Moiety Inverse agonist Corepressor |
| Zdroj: | ACS Medicinal Chemistry Letters. 9:120-124 |
| ISSN: | 1948-5875 |
| DOI: | 10.1021/acsmedchemlett.7b00476 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|