4wlb
From Proteopedia
Crystal structure of RORc in complex with a partial inverse agonist compound
Structural highlights
FunctionRORG_HUMAN Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. Publication Abstract from PubMedThe identification of a new series of RORc inverse agonists is described. Comprehensive structure-activity relationship studies of this reversed sulfonamide series identified potent RORc inverse agonists in biochemical and cellular assays which were also selective against a panel of nuclear receptors. Our work has contributed a compound that may serve as a useful in vitro tool to delineate the complex biological pathways involved in signalling through RORc. An X-ray co-crystal structure of an analogue with RORc has also provided useful insights into the binding interactions of the new series. A reversed sulfonamide series of selective RORc inverse agonists.,van Niel MB, Fauber BP, Cartwright M, Gaines S, Killen JC, Rene O, Ward SI, de Leon Boenig G, Deng Y, Eidenschenk C, Everett C, Gancia E, Ganguli A, Gobbi A, Hawkins J, Johnson AR, Kiefer JR, La H, Lockey P, Norman M, Ouyang W, Qin A, Wakes N, Waszkowycz B, Wong H Bioorg Med Chem Lett. 2014 Dec 15;24(24):5769-76. doi:, 10.1016/j.bmcl.2014.10.037. Epub 2014 Oct 25. PMID:25453817[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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