5LWP

Discovery of phenoxyindazoles and phenylthioindazoles as RORg inverse agonists

5LWP の概要

• エントリーDOI: 10.2210/pdb5lwp/pdb
• 分子名称: Nuclear receptor ROR-gamma, 4-[3-[2-chloranyl-6-(trifluoromethyl)phenoxy]-5-(dimethylcarbamoyl)indazol-1-yl]benzoic acid (3 entities in total)
• 機能のキーワード: ror gamma allosteric ligand inverse agonistm, 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: 1
• 化学式量合計: 28993.94

構造登録者

Ouvry, G.,Bouix-Peter, C.,Ciesielski, F.,Chantalat, L.,Christin, O.,Comino, C.,Duvert, D.,Feret, C.,Harris, C.S.,Luzy, A.-P.,Musicki, B.,Orfila, D.,Pascau, J.,Parnet, V.,Perrin, A.,Pierre, R.,Raffin, C.,Rival, Y.,Taquet, N.,Thoreau, E.,Hennequin, L.F. (登録日: 2016-09-19, 公開日: 2016-11-16, 最終更新日: 2024-11-20)

主引用文献

Ouvry, G.,Bouix-Peter, C.,Ciesielski, F.,Chantalat, L.,Christin, O.,Comino, C.,Duvert, D.,Feret, C.,Harris, C.S.,Lamy, L.,Luzy, A.P.,Musicki, B.,Orfila, D.,Pascau, J.,Parnet, V.,Perrin, A.,Pierre, R.,Polge, G.,Raffin, C.,Rival, Y.,Taquet, N.,Thoreau, E.,Hennequin, L.F.
Discovery of phenoxyindazoles and phenylthioindazoles as ROR gamma inverse agonists.
Bioorg.Med.Chem.Lett., 26:5802-5808, 2016

PubMed Abstract: Targeting the IL17 pathway and more specifically the nuclear receptor RORγ is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of phenoxyindazoles and thiophenoxy indazoles as potent RORγ inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models.

PubMed: 27815118
DOI: 10.1016/j.bmcl.2016.10.023

実験手法

X-RAY DIFFRACTION (2.4 Å)