7q6w
From Proteopedia
(Difference between revisions)
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==Crystal structure of the bromodomain of ATAD2 with triazolopyridazine (cpd 22)== | ==Crystal structure of the bromodomain of ATAD2 with triazolopyridazine (cpd 22)== | ||
| - | <StructureSection load='7q6w' size='340' side='right'caption='[[7q6w]]' scene=''> | + | <StructureSection load='7q6w' size='340' side='right'caption='[[7q6w]], [[Resolution|resolution]] 1.96Å' 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=7Q6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q6W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7q6w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q6W FirstGlance]. <br> |
| - | </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=7q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q6w OCA], [https://pdbe.org/7q6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q6w RCSB], [https://www.ebi.ac.uk/pdbsum/7q6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q6w 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=93L:(1R,9S)-13-[[3-methyl-8-[(1-methylpiperidin-4-yl)amino]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]carbonyl]-11,13-diazatricyclo[7.3.1.0^{2,7}]trideca-2,4,6-trien-10-one'>93L</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Adenosinetriphosphatase Adenosinetriphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.3 3.6.1.3] </span></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=7q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q6w OCA], [https://pdbe.org/7q6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q6w RCSB], [https://www.ebi.ac.uk/pdbsum/7q6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q6w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/ATAD2_HUMAN ATAD2_HUMAN]] May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells.<ref>PMID:17998543</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncology target. While several small molecule inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound 5 (AZ13824374), a highly potent and selective ATAD2 inhibitor which shows cellular target engagement and antiproliferative activity in a range of breast cancer models. | ||
| + | |||
| + | Discovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models.,Winter-Holt JJ, Bardelle C, Chiarparin E, Dale IL, Davey PRJ, Davies NL, Denz C, Fillery SM, Guerot CM, Han F, Hughes SJ, Kulkarni M, Liu Z, Milbradt A, Moss TA, Niu H, Patel J, Rabow AA, Schimpl M, Shi J, Sun D, Yang D, Guichard S J Med Chem. 2022 Feb 8. doi: 10.1021/acs.jmedchem.1c01871. PMID:35133824<ref>PMID:35133824</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7q6w" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Adenosinetriphosphatase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Patel | + | [[Category: Patel, S J]] |
| - | [[Category: Winter-Holt | + | [[Category: Winter-Holt, J J]] |
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Epigenetic]] | ||
| + | [[Category: Gene regulation]] | ||
Revision as of 11:08, 16 February 2022
Crystal structure of the bromodomain of ATAD2 with triazolopyridazine (cpd 22)
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