4XT9

RORgamma (263-509) complexed with GSK2435341A and SRC2

4XT9 の概要

• エントリーDOI: 10.2210/pdb4xt9/pdb
• 分子名称: Nuclear receptor ROR-gamma, LYS-ILE-LEU-HIS-ARG-LEU-LEU-GLN, N-[4-(2,5-dichlorophenyl)-5-phenyl-1,3-thiazol-2-yl]-2-[4-(ethylsulfonyl)phenyl]acetamide, ... (5 entities in total)
• 機能のキーワード: unknown protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : P51449
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30054.72

構造登録者

Wang, Y.,Ma, Y. (登録日: 2015-01-23, 公開日: 2015-08-12, 最終更新日: 2023-11-08)

主引用文献

Wang, Y.,Yang, T.,Liu, Q.,Ma, Y.,Yang, L.,Zhou, L.,Xiang, Z.,Cheng, Z.,Lu, S.,Orband-Miller, L.A.,Zhang, W.,Wu, Q.,Zhang, K.,Li, Y.,Xiang, J.N.,Elliott, J.D.,Leung, S.,Ren, F.,Lin, X.
Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent ROR gamma t inverse agonists
Bioorg.Med.Chem., 23:5293-5302, 2015

PubMed Abstract: A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORγt inverse agonists was discovered. Binding mode analysis of a RORγt partial agonist (2c) revealed by co-crystal structure in RORγt LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORγt LBD. Detailed SAR exploration led to identification of potent RORγt inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes.

PubMed: 26277758
DOI: 10.1016/j.bmc.2015.07.068

実験手法

X-RAY DIFFRACTION (2.25 Å)