6B30

Structure of RORgt in complex with a novel inverse agonist 1

6B30 の概要

• エントリーDOI: 10.2210/pdb6b30/pdb
• 分子名称: Nuclear receptor ROR-gamma, N-[(1R)-1-(4-methoxyphenyl)-2-oxo-2-{[4-(trimethylsilyl)phenyl]amino}ethyl]-N-methyl-3-oxo-2,3-dihydro-1,2-oxazole-5-carboxamide (3 entities in total)
• 機能のキーワード: complex, inverse agonist, nuclear hormone receptor, signaling protein
• 由来する生物種: Homo sapiens (Human)
• 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: 50908.96

構造登録者

Skene, R.J.,Hoffman, I. (登録日: 2017-09-20, 公開日: 2018-01-03, 最終更新日: 2024-03-13)

主引用文献

Shirai, J.,Tomata, Y.,Kono, M.,Ochida, A.,Fukase, Y.,Sato, A.,Masada, S.,Kawamoto, T.,Yonemori, K.,Koyama, R.,Nakagawa, H.,Nakayama, M.,Uga, K.,Shibata, A.,Koga, K.,Okui, T.,Shirasaki, M.,Skene, R.,Sang, B.,Hoffman, I.,Lane, W.,Fujitani, Y.,Yamasaki, M.,Yamamoto, S.
Discovery of orally efficacious ROR gamma t inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds.
Bioorg. Med. Chem., 26:483-500, 2018

PubMed Abstract: A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of RORγt in a mouse PD (pharmacodynamic) model upon oral administration.

PubMed: 29262987
DOI: 10.1016/j.bmc.2017.12.006

実験手法

X-RAY DIFFRACTION (2.69 Å)