6R7J

Ligand complex of RORg LBD

Summary for 6R7J

• Entry DOI: 10.2210/pdb6r7j/pdb
• Descriptor: Nuclear receptor ROR-gamma, SRC2 peptide, (2~{R})-2-acetamido-2-(4-ethylsulfonylphenyl)-~{N}-[4-[1,1,1,3,3,3-hexakis(fluoranyl)-2-oxidanyl-propan-2-yl]phenyl]ethanamide, ... (6 entities in total)
• Functional Keywords: rar-related orphan receptor-g (rorg), transcription, rorg ligand, structure-based design
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 35375.52

Authors

Xue, Y.,Aagaard, A.,Narjes, F. (deposition date: 2019-03-29, release date: 2019-07-03, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.84 Å)