5uew - Revision history

OCA at 14:26, 6 March 2024

OCA — Wed, 06 Mar 2024 14:26:44 GMT

←Older revision		Revision as of 14:26, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5uew' size='340' side='right'caption='[[5uew]], [[Resolution\|resolution]] 1.83Å' scene=''>		<StructureSection load='5uew' size='340' side='right'caption='[[5uew]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uew]] is a 2 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=5UEW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5UEW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uew]] 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=5UEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UEW FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=87D:N~~-[~~3-(4-METHOXY-~~1~~-METHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-4-PHENOXYPHENYL]METHANESULFONAMIDE'>87D</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]] 1.83Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5ueu\|5ueu]], [[5uf0\|5uf0]], [[5uez\|5uez]], [[5uey\|5uey]], [[5uex\|5uex]], [[5uev\|5uev]], [[5uep\|5uep]], [[5uet\|5uet]], [[5ues\|5ues]], [[5uer\|5uer]], [[5ueq\|5ueq]], [[5ueo\|5ueo]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=87D:N-[3-(4-METHOXY-1-METHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-4-PHENOXYPHENYL]METHANESULFONAMIDE'>87D</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><~~b>[[Gene\|Gene~~:]~~]</b~~></td>~~<td class="sblockDat">BRD2, KIAA9001, RING3 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5uew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uew OCA], [https://pdbe.org/5uew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uew RCSB], [https://www.ebi.ac.uk/pdbsum/5uew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uew ProSAT]</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=5uew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uew OCA], [~~http~~://pdbe.org/5uew PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5uew RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5uew PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5uew ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>	+	[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 muM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.	+
-		+
-	Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.,Wang L, Pratt JK, Soltwedel T, Sheppard GS, Fidanze SD, Liu D, Hasvold LA, Mantei RA, Holms JH, McClellan WJ, Wendt MD, Wada C, Frey R, Hansen TM, Hubbard R, Park CH, Li L, Magoc TJ, Albert DH, Lin X, Warder SE, Kovar P, Huang X, Wilcox D, Wang R, Rajaraman G, Petros AM, Hutchins CW, Panchal SC, Sun C, Elmore SW, Shen Y, Kati WM, McDaniel KF J Med Chem. 2017 Apr 21. doi: 10.1021/acs.jmedchem.7b00017. PMID:28368119<ref>PMID:28368119</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5uew" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Park~~, C H]]~~	+	[[Category: Park CH]]
-	~~[[Category: Signaling protein-inhibitor complex~~]]	+

OCA at 12:34, 23 September 2020

OCA — Wed, 23 Sep 2020 12:34:35 GMT

←Older revision		Revision as of 12:34, 23 September 2020
Line 1:		Line 1:

	==BRD2 Bromodomain2 with A-1360579==		==BRD2 Bromodomain2 with A-1360579==
-	<StructureSection load='5uew' size='340' side='right' caption='[[5uew]], [[Resolution\|resolution]] 1.83Å' scene=''>	+	<StructureSection load='5uew' size='340' side='right'caption='[[5uew]], [[Resolution\|resolution]] 1.83Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uew]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UEW OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UEW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uew]] is a 2 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=5UEW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UEW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=87D:N-[3-(4-METHOXY-1-METHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-4-PHENOXYPHENYL]METHANESULFONAMIDE'>87D</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=87D:N-[3-(4-METHOXY-1-METHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-4-PHENOXYPHENYL]METHANESULFONAMIDE'>87D</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ueu\|5ueu]], [[5uf0\|5uf0]], [[5uez\|5uez]], [[5uey\|5uey]], [[5uex\|5uex]], [[5uev\|5uev]], [[5uep\|5uep]], [[5uet\|5uet]], [[5ues\|5ues]], [[5uer\|5uer]], [[5ueq\|5ueq]], [[5ueo\|5ueo]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ueu\|5ueu]], [[5uf0\|5uf0]], [[5uez\|5uez]], [[5uey\|5uey]], [[5uex\|5uex]], [[5uev\|5uev]], [[5uep\|5uep]], [[5uet\|5uet]], [[5ues\|5ues]], [[5uer\|5uer]], [[5ueq\|5ueq]], [[5ueo\|5ueo]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5uew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uew OCA], [http://pdbe.org/5uew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uew RCSB], [http://www.ebi.ac.uk/pdbsum/5uew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uew ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([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=5uew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uew OCA], [http://pdbe.org/5uew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uew RCSB], [http://www.ebi.ac.uk/pdbsum/5uew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uew ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5uew" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5uew" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Park, C H]]		[[Category: Park, C H]]
	[[Category: Signaling protein-inhibitor complex]]		[[Category: Signaling protein-inhibitor complex]]

OCA at 12:50, 10 May 2017

OCA — Wed, 10 May 2017 12:50:13 GMT

←Older revision		Revision as of 12:50, 10 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5uew is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==BRD2 Bromodomain2 with A-1360579==
		+	<StructureSection load='5uew' size='340' side='right' caption='[[5uew]], [[Resolution\|resolution]] 1.83Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5uew]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UEW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=87D:N-[3-(4-METHOXY-1-METHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-4-PHENOXYPHENYL]METHANESULFONAMIDE'>87D</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ueu\|5ueu]], [[5uf0\|5uf0]], [[5uez\|5uez]], [[5uey\|5uey]], [[5uex\|5uex]], [[5uev\|5uev]], [[5uep\|5uep]], [[5uet\|5uet]], [[5ues\|5ues]], [[5uer\|5uer]], [[5ueq\|5ueq]], [[5ueo\|5ueo]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5uew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uew OCA], [http://pdbe.org/5uew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uew RCSB], [http://www.ebi.ac.uk/pdbsum/5uew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uew ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 muM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.

-	~~Authors~~:	+	Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.,Wang L, Pratt JK, Soltwedel T, Sheppard GS, Fidanze SD, Liu D, Hasvold LA, Mantei RA, Holms JH, McClellan WJ, Wendt MD, Wada C, Frey R, Hansen TM, Hubbard R, Park CH, Li L, Magoc TJ, Albert DH, Lin X, Warder SE, Kovar P, Huang X, Wilcox D, Wang R, Rajaraman G, Petros AM, Hutchins CW, Panchal SC, Sun C, Elmore SW, Shen Y, Kati WM, McDaniel KF J Med Chem. 2017 Apr 21. doi: 10.1021/acs.jmedchem.7b00017. PMID:28368119<ref>PMID:28368119</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5uew" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Park, C H]]
		+	[[Category: Signaling protein-inhibitor complex]]

OCA at 11:03, 5 April 2017

OCA — Wed, 05 Apr 2017 11:03:32 GMT

←Older revision		Revision as of 11:03, 5 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5uew is ON HOLD until ~~Jan 03 2019~~	+	The entry 5uew is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 14:24, 9 March 2017

OCA — Thu, 09 Mar 2017 14:24:36 GMT

←Older revision		Revision as of 14:24, 9 March 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5uew is ON HOLD	+	The entry 5uew is ON HOLD until Jan 03 2019

	Authors:		Authors:

OCA: Protected "5uew" [edit=sysop:move=sysop]

OCA — Wed, 18 Jan 2017 14:46:27 GMT

Protected "5uew" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:46, 18 January 2017

OCA: New page: '''Unreleased structure''' The entry 5uew is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Jan 2017 14:46:26 GMT

New page: '''Unreleased structure''' The entry 5uew is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5uew is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]