4NB6

Crystal structure of the ligand binding domain of RORC with T0901317

Summary for 4NB6

• Entry DOI: 10.2210/pdb4nb6/pdb
• Related: 1PQ9 1PQC 2O91
• Descriptor: Nuclear receptor ROR-gamma, N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE (3 entities in total)
• Functional Keywords: alpha-helical, transcription factor, nucleus, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): P51449
• Total number of polymer chains: 2
• Total formula weight: 59045.75

Authors

Hymowitz, S.G.,Boenig-de Leon, G. (deposition date: 2013-10-22, release date: 2013-11-27, Last modification date: 2023-09-20)

Primary citation

Fauber, B.P.,de Leon Boenig, G.,Burton, B.,Eidenschenk, C.,Everett, C.,Gobbi, A.,Hymowitz, S.G.,Johnson, A.R.,Liimatta, M.,Lockey, P.,Norman, M.,Ouyang, W.,Rene, O.,Wong, H.
Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc.
Bioorg.Med.Chem.Lett., 23:6604-6609, 2013

PubMed Abstract: The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.

PubMed: 24239186
DOI: 10.1016/j.bmcl.2013.10.054

Experimental method

X-RAY DIFFRACTION (2.85 Å)