5EC9

Retinoic acid receptor alpha in complex with chiral dihydrobenzofuran benzoic acid 9a and a fragment of the coactivator TIF2

Summary for 5EC9

• Entry DOI: 10.2210/pdb5ec9/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, LYS-HIS-LYS-ILE-LEU-HIS-ARG-LEU-LEU-GLN-ASP, 4-[(11S,15R)-4,4,7,7-Tetramethyl-16-oxatetracyclo[8.6.0.03,8.011,15]hexadeca-1(10),2,8-trien-11-yl]benzoic acid, ... (4 entities in total)
• Functional Keywords: transcription, nuclear receptor, agonist
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P19793
• Total number of polymer chains: 2
• Total formula weight: 25460.84

Authors

Leysen, S.,Ottmann, C.,Schafer, A.,Scheepstra, M.,Brunsveld, L.,Sunden, R.,Ma, J.N.,Burnstein, E.S.,Olsson, R. (deposition date: 2015-10-20, release date: 2016-03-09, Last modification date: 2024-06-19)

Primary citation

Sunden, H.,Schafer, A.,Scheepstra, M.,Leysen, S.,Malo, M.,Ma, J.N.,Burstein, E.S.,Ottmann, C.,Brunsveld, L.,Olsson, R.
Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.
J.Med.Chem., 59:1232-1238, 2016

PubMed Abstract: The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR-Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to the full agonist 9a at RXR (pEC50 of 8.2) and RXR-Nurr1. The X-ray structure shows enantiomeric discrimination where 9a optimally addresses the ligand binding pocket of RXR.

PubMed: 26820900
DOI: 10.1021/acs.jmedchem.5b01702

Experimental method

X-RAY DIFFRACTION (2.3 Å)