7q6w - Revision history

OCA at 07:53, 1 May 2024

OCA — Wed, 01 May 2024 07:53:11 GMT

←Older revision		Revision as of 07:53, 1 May 2024
Line 3:		Line 3:
	<StructureSection load='7q6w' size='340' side='right'caption='[[7q6w]], [[Resolution\|resolution]] 1.96Å' scene=''>		<StructureSection load='7q6w' size='340' side='right'caption='[[7q6w]], [[Resolution\|resolution]] 1.96Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<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>	+	<table><tr><td colspan='2'>[[7q6w]] is a 1 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=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='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>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.96Å</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='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='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>		<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 ==		== 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>	+	[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>	+	==See Also==
-		+	*[[ATPase family AAA domain-containing protein\|ATPase family AAA domain-containing protein]]
-	~~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 ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Adenosinetriphosphatase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Patel~~, S J~~]]	+	[[Category: Patel SJ]]
-	[[Category: Winter-Holt~~, J J]]~~	+	[[Category: Winter-Holt JJ]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Epigenetic]]~~	+
-	~~[[Category: Gene regulation~~]]	+

OCA at 11:08, 16 February 2022

OCA — Wed, 16 Feb 2022 11:08:15 GMT

←Older revision		Revision as of 11:08, 16 February 2022
Line 1:		Line 1:

	==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 SJ]]	+	[[Category: Patel, S J]]
-	[[Category: Winter-Holt JJ]]	+	[[Category: Winter-Holt, J J]]
		+	[[Category: Bromodomain]]
		+	[[Category: Epigenetic]]
		+	[[Category: Gene regulation]]

OCA at 07:30, 19 January 2022

OCA — Wed, 19 Jan 2022 07:30:37 GMT

←Older revision		Revision as of 07:30, 19 January 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7q6w ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of the bromodomain of ATAD2 with triazolopyridazine (cpd 22)==
-		+	<StructureSection load='7q6w' size='340' side='right'caption='[[7q6w]]' scene=''>
-	~~Authors~~:	+	== 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>
-	~~Description~~:	+	</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>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Patel SJ]]
		+	[[Category: Winter-Holt JJ]]

OCA: Protected "7q6w" [edit=sysop:move=sysop]

OCA — Wed, 17 Nov 2021 12:04:42 GMT

Protected "7q6w" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:04, 17 November 2021

OCA: New page: '''Unreleased structure''' The entry 7q6w is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Nov 2021 12:04:41 GMT

New page: '''Unreleased structure''' The entry 7q6w is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7q6w is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]