6w9h
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='6w9h' size='340' side='right'caption='[[6w9h]]' scene=''> | + | <StructureSection load='6w9h' size='340' side='right'caption='[[6w9h]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W9H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W9H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w9h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W9H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W9H 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=6w9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9h OCA], [http://pdbe.org/6w9h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9h RCSB], [http://www.ebi.ac.uk/pdbsum/6w9h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9h 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=TKJ:4-{(3R)-3-[4-(benzyloxy)phenyl]-3-[(4-fluorophenyl)sulfonyl]pyrrolidine-1-carbonyl}-1lambda~6~-thiane-1,1-dione'>TKJ</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCOA1, BHLHE74, SRC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></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=6w9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9h OCA], [http://pdbe.org/6w9h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9h RCSB], [http://www.ebi.ac.uk/pdbsum/6w9h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9h 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 6w9h" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Histone acetyltransferase]] | ||
| + | [[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 06:02, 13 May 2020
SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T AGONISTS
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