4qm0 | pdb_00004qm0

Crystal structure of RORc in complex with a tertiary sulfonamide inverse agonist

spinqualitylabelsall models 4qm0, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qm0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 39K, DMS Gene: RORC, NR1F3, RORG, RZRG (HUMAN) 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 Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma-protein unbound fraction and improvements in cellular permeability and aqueous solubility. Reduction in lipophilicity improved the solubility, plasma-protein binding, and permeability of tertiary sulfonamide RORc inverse agonists.,Fauber BP, Rene O, de Leon Boenig G, Burton B, Deng Y, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, La H, Liimatta M, Lockey P, Norman M, Ouyang W, Wang W, Wong H Bioorg Med Chem Lett. 2014 Aug 15;24(16):3891-7. doi: 10.1016/j.bmcl.2014.06.048., Epub 2014 Jun 25. PMID:25017032 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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