4ZOM

RORgamma in complex with inverse agonist 4j.

4ZOM の概要

• エントリーDOI: 10.2210/pdb4zom/pdb
• 分子名称: Nuclear receptor ROR-gamma, N-{4-[3-(acetylamino)-1-(propan-2-yl)-1H-pyrazol-5-yl]-2-[(1R,5S)-3-azabicyclo[3.1.0]hex-3-yl]phenyl}-2-chloro-6-fluoro-N-methylbenzamide (3 entities in total)
• 機能のキーワード: rorgamma inverse agonist, transcription
• 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: 4
• 化学式量合計: 106680.94

構造登録者

Marcotte, D.J. (登録日: 2015-05-06, 公開日: 2015-06-17, 最終更新日: 2023-09-27)

主引用文献

Wang, T.,Banerjee, D.,Bohnert, T.,Chao, J.,Enyedy, I.,Fontenot, J.,Guertin, K.,Jones, H.,Lin, E.Y.,Marcotte, D.,Talreja, T.,Van Vloten, K.
Discovery of novel pyrazole-containing benzamides as potent ROR gamma inverse agonists.
Bioorg.Med.Chem.Lett., 25:2985-2990, 2015

PubMed Abstract: The nuclear receptor RORγ plays a central role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including TH17 cells. RORγ-dependent inflammation has been implicated in the pathogenesis of several major autoimmune diseases and thus RORγ is an attractive target for therapeutic intervention in these diseases. Starting from a lead biaryl compound 4a, replacement of the head phenyl moiety with a substituted aminopyrazole group resulted in a series with improved physical properties. Further SAR exploration led to analogues (e.g., 4j and 5m) as potent RORγ inverse agonists.

PubMed: 26048789
DOI: 10.1016/j.bmcl.2015.05.028

実験手法

X-RAY DIFFRACTION (2.27 Å)