6xae
From Proteopedia
(Difference between revisions)
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==SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T AGONISTS== | ==SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T AGONISTS== | ||
| - | <StructureSection load='6xae' size='340' side='right'caption='[[6xae]]' scene=''> | + | <StructureSection load='6xae' size='340' side='right'caption='[[6xae]], [[Resolution|resolution]] 2.26Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6w9j 6w9j]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XAE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xae]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6w9j 6w9j]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XAE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XAE FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xae OCA], [http://pdbe.org/6xae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xae RCSB], [http://www.ebi.ac.uk/pdbsum/6xae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xae ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Z7F:trans-4-{(3aR,9bR)-7-[(2-chloro-6-fluorophenyl)methoxy]-9b-[(4-fluorophenyl)sulfonyl]-1,2,3a,4,5,9b-hexahydro-3H-benzo[e]indole-3-carbonyl}cyclohexane-1-carboxylic+acid'>Z7F</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6xae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xae OCA], [http://pdbe.org/6xae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xae RCSB], [http://www.ebi.ac.uk/pdbsum/6xae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xae ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Substituted benzyloxy aryl compound 2 was identified as an RORgammat agonist. Structure based drug design efforts resulted in a potent and selective tricyclic compound 19 which, when administered orally in an MC38 mouse tumor model, demonstrated a desired pharmacokinetic profile as well as a dose-dependent pharmacodynamic response. However, no perceptible efficacy was observed in this tumor model at the doses investigated. | ||
| + | |||
| + | Substituted benzyloxytricyclic compounds as retinoic acid-related orphan receptor gamma t (RORgammat) agonists.,Harikrishnan LS, Gill P, Kamau MG, Qin LY, Ruan Z, O'Malley D, Huynh T, Stachura S, Cavallaro CL, Lu Z, J-W Duan J, Weigelt CA, Sack JS, Ruzanov M, Khan J, Gururajan M, Wong JJ, Huang Y, Yarde M, Li Z, Chen C, Sun H, Borowski V, Murtaza A, Fink BE Bioorg Med Chem Lett. 2020 Jun 15;30(12):127204. doi: 10.1016/j.bmcl.2020.127204., Epub 2020 Apr 20. PMID:32334911<ref>PMID:32334911</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6xae" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Sack | + | [[Category: Sack, J S]] |
| + | [[Category: Inve agonist]] | ||
| + | [[Category: Ligand-binding domain]] | ||
| + | [[Category: Nuclear hormone receptor]] | ||
| + | [[Category: Rorgt]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 07:18, 25 June 2020
SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T AGONISTS
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