6Q2W

Crystal structure of human ROR gamma LBD in complex with a quinoline sulfonamide inverse agonist

6Q2W の概要

• エントリーDOI: 10.2210/pdb6q2w/pdb
• 分子名称: Nuclear receptor ROR-gamma, (2~{S})-1-[2,4-bis(chloranyl)-3-[[4-imidazol-1-yl-2-(trifluoromethyl)quinolin-8-yl]oxymethyl]phenyl]sulfonyl-~{N}-methyl-pyrrolidine-2-carboxamide (3 entities in total)
• 機能のキーワード: ror gamma, inverse agonist, nuclear hormone receptor, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52972.80

構造登録者

Ciesielski, F.,Amaudrut, J.,Argiriadi, M.A.,Barth, M.,Breinlinger, E.C.,Calderwood, D.J.,Cusack, K.P.,Kort, M.E.,Montalbetti, C.,Potin, D.,Poupardin, O.,Spitzer, L. (登録日: 2018-12-03, 公開日: 2019-05-29, 最終更新日: 2024-01-24)

主引用文献

Amaudrut, J.,Argiriadi, M.A.,Barth, M.,Breinlinger, E.C.,Bressac, D.,Broqua, P.,Calderwood, D.J.,Chatar, M.,Cusack, K.P.,Gauld, S.B.,Jacquet, S.,Kamath, R.V.,Kort, M.E.,Lepais, V.,Luccarini, J.M.,Masson, P.,Montalbetti, C.,Mounier, L.,Potin, D.,Poupardin, O.,Rouaud, S.,Spitzer, L.,Wallace, C.D.
Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active ROR gamma inverse agonists.
Bioorg.Med.Chem.Lett., 29:1799-1806, 2019

PubMed Abstract: A high-throughput screen against Inventiva's compound library using a Gal4/RORγ-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORγ inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein.

PubMed: 31101472
DOI: 10.1016/j.bmcl.2019.05.015

実験手法

X-RAY DIFFRACTION (1.99 Å)