6q2w

Crystal structure of human ROR gamma LBD in complex with a quinoline sulfonamide inverse agonist

spinqualitylabelsall models 6q2w, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q2w is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.99Å Ligands: HBW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RORG_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 PubMed A high-throughput screen against Inventiva's compound library using a Gal4/RORgamma-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORgamma inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein. Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORgamma inverse agonists.,Amaudrut J, Argiriadi MA, Barth M, Breinlinger EC, Bressac D, Broqua P, Calderwood DJ, Chatar M, Cusack KP, Gauld SB, Jacquet S, Kamath RV, Kort ME, Lepais V, Luccarini JM, Masson P, Montalbetti C, Mounier L, Potin D, Poupardin O, Rouaud S, Spitzer L, Wallace CD Bioorg Med Chem Lett. 2019 May 9. pii: S0960-894X(19)30301-4. doi:, 10.1016/j.bmcl.2019.05.015. PMID:31101472 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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