6R7A

Ligand complex of RORg LBD

6R7A の概要

• エントリーDOI: 10.2210/pdb6r7a/pdb
• 分子名称: Nuclear receptor ROR-gamma, LYS-HIS-LYS-ILE-LEU-HIS-ARG-LEU-LEU-GLN-ASP-SER, ~{N}-[(1~{R})-1-(4-methoxyphenyl)-2-oxidanylidene-2-[(4-propan-2-ylphenyl)amino]ethyl]-2-oxidanylidene-3~{H}-pyridine-5-carboxamide, ... (5 entities in total)
• 機能のキーワード: rar-related orphan receptor-g (rorg), transcription, rorg ligand, structure-based design
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35190.41

構造登録者

Xue, Y.,Aagaard, A.,Narjes, F. (登録日: 2019-03-28, 公開日: 2019-07-03, 最終更新日: 2024-05-15)

主引用文献

von Berg, S.,Xue, Y.,Collins, M.,Llinas, A.,Olsson, R.I.,Halvarsson, T.,Lindskog, M.,Malmberg, J.,Jirholt, J.,Krutrok, N.,Ramnegard, M.,Brannstrom, M.,Lundqvist, A.,Lepisto, M.,Aagaard, A.,McPheat, J.,Hansson, E.L.,Chen, R.,Xiong, Y.,Hansson, T.G.,Narjes, F.
Discovery of Potent and Orally Bioavailable Inverse Agonists of the Retinoic Acid Receptor-Related Orphan Receptor C2.
Acs Med.Chem.Lett., 10:972-977, 2019

PubMed Abstract: The further optimization of a recently disclosed series of inverse agonists of the nuclear receptor RORC2 is described. Investigations into the left-hand side of compound , guided by X-ray crystal structures, led to the substitution of the 4-aryl-thiophenyl residue with the hexafluoro-2-phenyl-propan-2-ol moiety. This change resulted in to compound , which combined improved drug-like properties with good cell potency and a significantly lower dose, using an early dose to man prediction. Target engagement was demonstrated in the thymus of mice by a reduction in the number of double positive T cells after oral dosing.

PubMed: 31223457
DOI: 10.1021/acsmedchemlett.9b00158

実験手法

X-RAY DIFFRACTION (2.13 Å)