4XT9

RORgamma (263-509) complexed with GSK2435341A and SRC2

Summary for 4XT9

• Entry DOI: 10.2210/pdb4xt9/pdb
• Descriptor: Nuclear receptor ROR-gamma, LYS-ILE-LEU-HIS-ARG-LEU-LEU-GLN, N-[4-(2,5-dichlorophenyl)-5-phenyl-1,3-thiazol-2-yl]-2-[4-(ethylsulfonyl)phenyl]acetamide, ... (5 entities in total)
• Functional Keywords: unknown protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P51449
• Total number of polymer chains: 2
• Total formula weight: 30054.72

Authors

Wang, Y.,Ma, Y. (deposition date: 2015-01-23, release date: 2015-08-12, Last modification date: 2023-11-08)

Primary citation

Wang, Y.,Yang, T.,Liu, Q.,Ma, Y.,Yang, L.,Zhou, L.,Xiang, Z.,Cheng, Z.,Lu, S.,Orband-Miller, L.A.,Zhang, W.,Wu, Q.,Zhang, K.,Li, Y.,Xiang, J.N.,Elliott, J.D.,Leung, S.,Ren, F.,Lin, X.
Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent ROR gamma t inverse agonists
Bioorg.Med.Chem., 23:5293-5302, 2015

PubMed Abstract: A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORγt inverse agonists was discovered. Binding mode analysis of a RORγt partial agonist (2c) revealed by co-crystal structure in RORγt LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORγt LBD. Detailed SAR exploration led to identification of potent RORγt inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes.

PubMed: 26277758
DOI: 10.1016/j.bmc.2015.07.068

Experimental method

X-RAY DIFFRACTION (2.25 Å)