6b30
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of RORgt in complex with a novel inverse agonist 1== | |
| + | <StructureSection load='6b30' size='340' side='right' caption='[[6b30]], [[Resolution|resolution]] 2.69Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6b30]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B30 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CFG:N-[(1R)-1-(4-methoxyphenyl)-2-oxo-2-{[4-(trimethylsilyl)phenyl]amino}ethyl]-N-methyl-3-oxo-2,3-dihydro-1,2-oxazole-5-carboxamide'>CFG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b30 OCA], [http://pdbe.org/6b30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b30 RCSB], [http://www.ebi.ac.uk/pdbsum/6b30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b30 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RORG_HUMAN 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (RORgammat) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of RORgammat in a mouse PD (pharmacodynamic) model upon oral administration. | ||
| - | + | Discovery of orally efficacious RORgammat inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds.,Shirai J, Tomata Y, Kono M, Ochida A, Fukase Y, Sato A, Masada S, Kawamoto T, Yonemori K, Koyama R, Nakagawa H, Nakayama M, Uga K, Shibata A, Koga K, Okui T, Shirasaki M, Skene R, Sang B, Hoffman I, Lane W, Fujitani Y, Yamasaki M, Yamamoto S Bioorg Med Chem. 2017 Dec 9. pii: S0968-0896(17)31989-2. doi:, 10.1016/j.bmc.2017.12.006. PMID:29262987<ref>PMID:29262987</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 6b30" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Hoffman, I]] | [[Category: Hoffman, I]] | ||
| - | [[Category: Skene, R | + | [[Category: Skene, R J]] |
| + | [[Category: Complex]] | ||
| + | [[Category: Inverse agonist]] | ||
| + | [[Category: Nuclear hormone receptor]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 05:51, 3 January 2018
Structure of RORgt in complex with a novel inverse agonist 1
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