6gwr - Revision history

OCA at 08:05, 29 August 2018

OCA — Wed, 29 Aug 2018 08:05:45 GMT

←Older revision		Revision as of 08:05, 29 August 2018
Line 33:		Line 33:
	[[Category: Kupinska, K]]		[[Category: Kupinska, K]]
	[[Category: Pinkas, D M]]		[[Category: Pinkas, D M]]
-	[[Category: ~~Ai domain]]~~	+	[[Category: Transferase]]
-	~~[[Category: Cct domain]]~~	+
-	~~[[Category: Peptide binding protein]]~~	+
-	~~[[Category: Rfxv motif binding]]~~	+
-	~~[[Category: Wnk2~~]]	+

OCA at 16:43, 15 August 2018

OCA — Wed, 15 Aug 2018 16:43:08 GMT

←Older revision		Revision as of 16:43, 15 August 2018
Line 3:		Line 3:
	<StructureSection load='6gwr' size='340' side='right' caption='[[6gwr]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='6gwr' size='340' side='right' caption='[[6gwr]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gwr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gwr]] 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=6GWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FEW:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-benzamide'>FEW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FEW:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-benzamide'>FEW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DDR1, CAK, EDDR1, NEP, NTRK4, PTK3A, RTK6, TRKE ([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/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=6gwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwr OCA], [http://pdbe.org/6gwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwr RCSB], [http://www.ebi.ac.uk/pdbsum/6gwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwr ProSAT]</span></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=6gwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwr OCA], [http://pdbe.org/6gwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwr RCSB], [http://www.ebi.ac.uk/pdbsum/6gwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwr ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Discoidin domain receptor 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to co-inhibit DDR1 and DDR2. One of the most promising compounds, 5n, tightly bound to DDR1 and DDR2 protein with Kd values of 7.9 and 8.0 nM, and potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively, while was significantly less potent for a panel of 403 wild-type kinases at 1.0 muM. DDR1 and DDR2 kinase inhibition by 5n was validated by Western blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) release in vitro, and exhibited promising in vivo anti-inflammatory effect in a LPS-induced acute lung injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.
		+
		+	Design, Synthesis and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)m ethyl)-5-(trifluoromethyl)phenyl)benzamide as Dual Inhibitors of Discoidin Domain Receptor 1 and 2 (DDR1/2).,Wang Z, Zhang Y, Pinkas D, Fox A, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q, Zhu D, Tu ZC, Ren X, Brekken RA, Bullock AN, Liang G, Ding K, Lu X J Med Chem. 2018 Aug 3. doi: 10.1021/acs.jmedchem.8b01045. PMID:30075624<ref>PMID:30075624</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gwr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]

OCA at 21:58, 9 August 2018

OCA — Thu, 09 Aug 2018 21:58:23 GMT

←Older revision		Revision as of 21:58, 9 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6gwr is ON HOLD~~	+	==Structure of the kinase domain of human DDR1 in complex with a potent and selective inhibitor of DDR1 and DDR2==
-		+	<StructureSection load='6gwr' size='340' side='right' caption='[[6gwr]], [[Resolution\|resolution]] 2.07Å' scene=''>
-	~~Authors: Pinkas, D.M., Fox, A.E., Kupinska, K., Burgess-Brown, N.A., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A.N.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gwr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GWR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GWR FirstGlance]. <br>
-	~~Description:~~ Structure of the kinase domain of human DDR1 in complex with a potent and selective inhibitor of DDR1 and DDR2	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FEW:3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-4-propan-2-yl-benzamide'>FEW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[~~Category: Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
-	[[~~Category: Fox, A.E~~]]	+	<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=6gwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gwr OCA], [http://pdbe.org/6gwr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gwr RCSB], [http://www.ebi.ac.uk/pdbsum/6gwr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gwr ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Arrowsmith, C~~.H]]	+	</table>
-	[[~~Category~~: ~~Burgess~~-~~Brown~~, N.A]]	+	__TOC__
-	[~~[Category~~: ~~Von Delft~~, F]]	+	</StructureSection>
-	[[~~Category~~: ~~Bullock~~, A.N]]	+	[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: ~~Pinkas, D.M~~]]	+	[[Category: Arrowsmith, C H]]
-	[[Category: ~~Edwards~~, ~~A.M~~]]	+
	[[Category: Bountra, C]]		[[Category: Bountra, C]]
		+	[[Category: Bullock, A N]]
		+	[[Category: Burgess-Brown, N A]]
		+	[[Category: Delft, F von]]
		+	[[Category: Edwards, A M]]
		+	[[Category: Fox, A E]]
	[[Category: Kupinska, K]]		[[Category: Kupinska, K]]
		+	[[Category: Pinkas, D M]]
		+	[[Category: Ai domain]]
		+	[[Category: Cct domain]]
		+	[[Category: Peptide binding protein]]
		+	[[Category: Rfxv motif binding]]
		+	[[Category: Wnk2]]

OCA: Protected "6gwr" [edit=sysop:move=sysop]

OCA — Wed, 04 Jul 2018 05:54:55 GMT

Protected "6gwr" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:54, 4 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gwr is ON HOLD Authors: Pinkas, D.M., Fox, A.E., Kupinska, K., Burgess-Brown, N.A., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bu...

OCA — Wed, 04 Jul 2018 05:54:54 GMT

New page: '''Unreleased structure''' The entry 6gwr is ON HOLD Authors: Pinkas, D.M., Fox, A.E., Kupinska, K., Burgess-Brown, N.A., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bu...

New page

'''Unreleased structure'''

The entry 6gwr is ON HOLD

Authors: Pinkas, D.M., Fox, A.E., Kupinska, K., Burgess-Brown, N.A., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A.N.

Description: Structure of the kinase domain of human DDR1 in complex with a potent and selective inhibitor of DDR1 and DDR2
[[Category: Unreleased Structures]]
[[Category: Fox, A.E]]
[[Category: Arrowsmith, C.H]]
[[Category: Burgess-Brown, N.A]]
[[Category: Von Delft, F]]
[[Category: Bullock, A.N]]
[[Category: Pinkas, D.M]]
[[Category: Edwards, A.M]]
[[Category: Bountra, C]]
[[Category: Kupinska, K]]