7ofi
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7ofi is ON HOLD Authors: Xue, Y., Aagaard, A., Narjes, F. Description: Ligand complex of RORg LBD Category: Unreleased Structures [[Category: A...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Ligand complex of RORg LBD== | |
| + | <StructureSection load='7ofi' size='340' side='right'caption='[[7ofi]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7ofi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OFI FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.953Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VCK:(2~{R})-2-(4-ethylsulfonylphenyl)-~{N}-[4-[1,1,1,3,3,3-hexakis(fluoranyl)-2-oxidanyl-propan-2-yl]phenyl]-~{N}-methyl-butanediamide'>VCK</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ofi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ofi OCA], [https://pdbe.org/7ofi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ofi RCSB], [https://www.ebi.ac.uk/pdbsum/7ofi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ofi ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://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 == | ||
| + | Inverse agonists of the nuclear receptor RORC2 have been widely pursued as a potential treatment for a variety of autoimmune diseases. We have discovered a novel series of isoindoline-based inverse agonists of the nuclear receptor RORC2, derived from our recently disclosed RORC2 inverse agonist 2. Extensive structure-activity relationship (SAR) studies resulted in AZD0284 (20), which combined potent inhibition of IL-17A secretion from primary human T(H)17 cells with excellent metabolic stability and good PK in preclinical species. In two preclinical in vivo studies, compound 20 reduced thymocyte numbers in mice and showed dose-dependent reduction of IL-17A containing gammadelta-T cells and of IL-17A and IL-22 RNA in the imiquimod induced inflammation model. Based on these data and a favorable safety profile, 20 was progressed to phase 1 clinical studies. | ||
| - | + | AZD0284, a Potent, Selective, and Orally Bioavailable Inverse Agonist of Retinoic Acid Receptor-Related Orphan Receptor C2.,Narjes F, Llinas A, von Berg S, Jirholt J, Lever S, Pehrson R, Collins M, Malmberg A, Svanberg P, Xue Y, Olsson RI, Malmberg J, Hughes G, Hossain N, Grindebacke H, Leffler A, Krutrok N, Back E, Ramnegard M, Lepisto M, Thunberg L, Aagaard A, McPheat J, Hansson EL, Chen R, Xiong Y, Hansson TG J Med Chem. 2021 Sep 23;64(18):13807-13829. doi: 10.1021/acs.jmedchem.1c01197. , Epub 2021 Aug 31. PMID:34464130<ref>PMID:34464130</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Aagaard | + | <div class="pdbe-citations 7ofi" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Aagaard A]] | ||
| + | [[Category: Narjes F]] | ||
| + | [[Category: Xue Y]] | ||
Current revision
Ligand complex of RORg LBD
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