5UHI

Structure of RORgt bound to

Summary for 5UHI

• Entry DOI: 10.2210/pdb5uhi/pdb
• Descriptor: Nuclear receptor ROR-gamma, (R)-(4-chloro-2-methoxy-3-{[4-(1H-pyrazol-1-yl)phenyl]methyl}quinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol (2 entities in total)
• Functional Keywords: nuclear hormone receptor, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P51449
• Total number of polymer chains: 2
• Total formula weight: 61346.31

Authors

Spurlino, J.,Abad, M. (deposition date: 2017-01-11, release date: 2017-04-05, Last modification date: 2024-03-06)

Primary citation

Kummer, D.A.,Cummings, M.D.,Abad, M.,Barbay, J.,Castro, G.,Wolin, R.,Kreutter, K.D.,Maharoof, U.,Milligan, C.,Nishimura, R.,Pierce, J.,Schalk-Hihi, C.,Spurlino, J.,Urbanski, M.,Venkatesan, H.,Wang, A.,Woods, C.,Xue, X.,Edwards, J.P.,Fourie, A.M.,Leonard, K.
Identification and structure activity relationships of quinoline tertiary alcohol modulators of ROR gamma t.
Bioorg. Med. Chem. Lett., 27:2047-2057, 2017

PubMed Abstract: A high-throughput screen of the ligand binding domain of the nuclear receptor retinoic acid-related orphan receptor gamma t (RORγt) employing a thermal shift assay yielded a quinoline tertiary alcohol hit. Optimization of the 2-, 3- and 4-positions of the quinoline core using structure-activity relationships and structure-based drug design methods led to the discovery of a series of modulators with improved RORγt inhibitory potency and inverse agonism properties.

PubMed: 28318945
DOI: 10.1016/j.bmcl.2017.02.044

Experimental method

X-RAY DIFFRACTION (3.198 Å)