5za1 | pdb_00005za1

Ligand complex of RORgt LBD

spinqualitylabelsall models 5za1, resolution 2.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5za1 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 2.52Å Ligands: 9A0, DMF, EDO 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 The retinoic acid receptor-related orphan receptor-gamma-t (RORgammat) is the master transcription factor responsible for regulating the development and function of T-helper 17 (Th17) cells, which are related to the pathology of several autoimmune disorders. Therefore, RORgammat is an attractive drug target for such Th17-mediated autoimmune diseases. A structure-activity relationship (SAR) study of lead compound 1 yielded a novel series of RORgammat inhibitors, represented by compound 6. Detailed SAR optimization, informed by X-ray cocrystal structure analysis, led to the discovery of a potent orally bioavailable RORgammat inhibitor 25, which inhibited IL-17 production in the skin of IL-23-treated mice by oral administration. Discovery of a potent orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORgammat) inhibitor, S18-000003.,Sasaki Y, Odan M, Yamamoto S, Kida S, Ueyama A, Shimizu M, Haruna T, Watanabe A, Okuno T Bioorg Med Chem Lett. 2018 Dec 1;28(22):3549-3553. doi:, 10.1016/j.bmcl.2018.09.032. Epub 2018 Sep 27. PMID:30301676 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA