5ceq - Revision history

OCA at 12:20, 6 March 2024

OCA — Wed, 06 Mar 2024 12:20:13 GMT

←Older revision		Revision as of 12:20, 6 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5ceq]] 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=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5ceq]] 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=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</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]] 1.911Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [https://pdbe.org/5ceq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [https://www.ebi.ac.uk/pdbsum/5ceq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ceq 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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [https://pdbe.org/5ceq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [https://www.ebi.ac.uk/pdbsum/5ceq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ceq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.		[https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small molecule DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein we describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochemical properties. We also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, we identified inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model.
-
-	Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).,Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y, Ma C, Scearce-Levie K, Ghosh AS, Shin YG, Solanoy H, Wang J, Wang B, Yin J, Siu M, Lewcock JW J Med Chem. 2015 Oct 2. PMID:26431428<ref>PMID:26431428</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5ceq" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 12:01, 14 June 2023

OCA — Wed, 14 Jun 2023 12:01:47 GMT

←Older revision		Revision as of 12:01, 14 June 2023
Line 3:		Line 3:
	<StructureSection load='5ceq' size='340' side='right'caption='[[5ceq]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='5ceq' size='340' side='right'caption='[[5ceq]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ceq]] 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=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ceq]] 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=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5cen\|5cen]], [[5ceo\|5ceo]], [[5cep\|5cep]]</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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [https://pdbe.org/5ceq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [https://www.ebi.ac.uk/pdbsum/5ceq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ceq ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP3K12, ZPK ([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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [~~http~~://pdbe.org/5ceq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ceq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ceq ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN]] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.	+	[https://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase kinase]]~~	+	[[Category: HARRIS SF]]
-	[[Category: HARRIS~~, S F~~]]	+	[[Category: YIN J]]
-	[[Category: YIN, J]]	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 11:35, 27 March 2020

OCA — Fri, 27 Mar 2020 11:35:18 GMT

←Older revision		Revision as of 11:35, 27 March 2020
Line 1:		Line 1:
		+
	==DLK in complex with inhibitor 2-((1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)amino)isonicotinonitrile==		==DLK in complex with inhibitor 2-((1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)amino)isonicotinonitrile==
-	<StructureSection load='5ceq' size='340' side='right' caption='[[5ceq]], [[Resolution\|resolution]] 1.91Å' scene=''>	+	<StructureSection load='5ceq' size='340' side='right'caption='[[5ceq]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ceq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ceq]] 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=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5cen\|5cen]], [[5ceo\|5ceo]], [[5cep\|5cep]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5cen\|5cen]], [[5ceo\|5ceo]], [[5cep\|5cep]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP3K12, ZPK ([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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [http://pdbe.org/5ceq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [http://www.ebi.ac.uk/pdbsum/5ceq PDBsum]</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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [http://pdbe.org/5ceq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [http://www.ebi.ac.uk/pdbsum/5ceq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ceq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 23:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: HARRIS, S F]]		[[Category: HARRIS, S F]]

OCA at 03:50, 16 October 2015

OCA — Fri, 16 Oct 2015 03:50:40 GMT

←Older revision		Revision as of 03:50, 16 October 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==DLK in complex with inhibitor 2-((1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)amino)isonicotinonitrile==
		+	<StructureSection load='5ceq' size='340' side='right' caption='[[5ceq]], [[Resolution\|resolution]] 1.91Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ceq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CEQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=50F:2-[[1-CYCLOPENTYL-5-[1-(OXETAN-3-YL)PIPERIDIN-4-YL]PYRAZOL-3-YL]AMINO]PYRIDINE-4-CARBONITRILE'>50F</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5cen\|5cen]], [[5ceo\|5ceo]], [[5cep\|5cep]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=5ceq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ceq OCA], [http://pdbe.org/5ceq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ceq RCSB], [http://www.ebi.ac.uk/pdbsum/5ceq PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K12_HUMAN M3K12_HUMAN]] May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small molecule DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein we describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochemical properties. We also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, we identified inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model.

-	~~The entry 5ceq is ON HOLD until Paper Publication~~	+	Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).,Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y, Ma C, Scearce-Levie K, Ghosh AS, Shin YG, Solanoy H, Wang J, Wang B, Yin J, Siu M, Lewcock JW J Med Chem. 2015 Oct 2. PMID:26431428<ref>PMID:26431428</ref>

-	~~Authors: HARRIS~~, S.~~F., YIN, J~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~:	+	<div class="pdbe-citations 5ceq" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
-	[[Category: ~~Yin~~, J]]	+	<references/>
-	[[Category: ~~Harris~~, ~~S.F~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
		+	[[Category: HARRIS, S F]]
		+	[[Category: YIN, J]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 18:29, 5 August 2015

OCA — Wed, 05 Aug 2015 18:29:44 GMT

←Older revision		Revision as of 18:29, 5 August 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ceq is ON HOLD	+	The entry 5ceq is ON HOLD until Paper Publication

	Authors: HARRIS, S.F., YIN, J.		Authors: HARRIS, S.F., YIN, J.

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

OCA — Wed, 15 Jul 2015 12:28:54 GMT

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

←Older revision

Revision as of 12:28, 15 July 2015

OCA: New page: '''Unreleased structure''' The entry 5ceq is ON HOLD Authors: HARRIS, S.F., YIN, J. Description: Category: Unreleased Structures Category: Yin, J Category: Harris, S.F

OCA — Wed, 15 Jul 2015 12:28:53 GMT

New page: '''Unreleased structure''' The entry 5ceq is ON HOLD Authors: HARRIS, S.F., YIN, J. Description: Category: Unreleased Structures Category: Yin, J Category: Harris, S.F

New page

'''Unreleased structure'''

The entry 5ceq is ON HOLD

Authors: HARRIS, S.F., YIN, J.

Description:
[[Category: Unreleased Structures]]
[[Category: Yin, J]]
[[Category: Harris, S.F]]