4ehz - Revision history

OCA at 07:12, 28 September 2022

OCA — Wed, 28 Sep 2022 07:12:24 GMT

←Older revision		Revision as of 07:12, 28 September 2022
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	==The Jak1 kinase domain in complex with inhibitor==		==The Jak1 kinase domain in complex with inhibitor==
-	<StructureSection load='4ehz' size='340' side='right' caption='[[4ehz]], [[Resolution\|resolution]] 2.17Å' scene=''>	+	<StructureSection load='4ehz' size='340' side='right'caption='[[4ehz]], [[Resolution\|resolution]] 2.17Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ehz]] is a 4 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=4EHZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EHZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ehz]] is a 4 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=4EHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHZ 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=JAK:2-METHYL-1-(PIPERIDIN-4-YL)-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE'>JAK</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JAK:2-METHYL-1-(PIPERIDIN-4-YL)-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE'>JAK</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=4ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehz OCA], [https://pdbe.org/4ehz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehz RCSB], [https://www.ebi.ac.uk/pdbsum/4ehz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehz ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehz OCA], [~~http~~://pdbe.org/4ehz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ehz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ehz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehz ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.	+	[[https://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Janus kinase\|Janus kinase]]	+	*[[Janus kinase 3D structures\|Janus kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific protein-tyrosine kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Lupardus~~, P J~~]]	+	[[Category: Lupardus PJ]]
-	[[Category: Steffek, M]]	+	[[Category: Steffek M]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 20:05, 4 August 2016

OCA — Thu, 04 Aug 2016 20:05:42 GMT

←Older revision		Revision as of 20:05, 4 August 2016
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		+
	==The Jak1 kinase domain in complex with inhibitor==		==The Jak1 kinase domain in complex with inhibitor==
	<StructureSection load='4ehz' size='340' side='right' caption='[[4ehz]], [[Resolution\|resolution]] 2.17Å' scene=''>		<StructureSection load='4ehz' size='340' side='right' caption='[[4ehz]], [[Resolution\|resolution]] 2.17Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ehz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ehz]] is a 4 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=4EHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHZ 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=JAK:2-METHYL-1-(PIPERIDIN-4-YL)-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE'>JAK</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=JAK:2-METHYL-1-(PIPERIDIN-4-YL)-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE'>JAK</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehz RCSB], [http://www.ebi.ac.uk/pdbsum/4ehz 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=4ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehz OCA], [http://pdbe.org/4ehz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ehz RCSB], [http://www.ebi.ac.uk/pdbsum/4ehz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4ehz" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Lupardus, P J]]		[[Category: Lupardus, P J]]

OCA at 19:07, 24 December 2014

OCA — Wed, 24 Dec 2014 19:07:58 GMT

←Older revision		Revision as of 19:07, 24 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4ehz.~~png~~\|~~left~~\|~~200px~~]]	+	==The Jak1 kinase domain in complex with inhibitor==
		+	<StructureSection load='4ehz' size='340' side='right' caption='[[4ehz]], [[Resolution\|resolution]] 2.17Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ehz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHZ 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=JAK:2-METHYL-1-(PIPERIDIN-4-YL)-1,6-DIHYDROIMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDINE'>JAK</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=4ehz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehz RCSB], [http://www.ebi.ac.uk/pdbsum/4ehz PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Herein we report the discovery of the C-2 methyl substituted imidazopyrrolopyridine series and its optimization to provide potent and orally bioavailable JAK1 inhibitors with selectivity over JAK2. The C-2 methyl substituted inhibitor 4 exhibited not only improved JAK1 potency relative to unsubstituted compound 3 but also notable JAK1 vs JAK2 selectivity (20-fold and >33-fold in biochemical and cell-based assays, respectively). Features of the X-ray structures of 4 in complex with both JAK1 and JAK2 are delineated. Efforts to improve the in vitro and in vivo ADME properties of 4 while maintaining JAK1 selectivity are described, culminating in the discovery of a highly optimized and balanced inhibitor (20). Details of the biological characterization of 20 are disclosed including JAK1 vs JAK2 selectivity levels, preclinical in vivo PK profiles, performance in an in vivo JAK1-mediated PK/PD model, and attributes of an X-ray structure in complex with JAK1.

-	~~{{STRUCTURE_4ehz\| PDB=4ehz \| SCENE= }}~~	+	Discovery and Optimization of C-2 Methyl Imidazopyrrolopyridines as Potent and Orally Bioavailable JAK1 Inhibitors with Selectivity over JAK2.,Zak M, Mendonca R, Balazs M, Barrett K, Bergeron P, Blair WS, Chang C, Deshmukh G, Devoss J, Dragovich PS, Eigenbrot C, Ghilardi N, Gibbons P, Gradl S, Hamman C, Hanan EJ, Harstad E, Hewitt PR, Hurley CA, Jin T, Johnson A, Johnson T, Kenny JR, Koehler MF, Bir Kohli P, Kulagowski JJ, Labadie S, Liao J, Liimatta M, Lin Z, Lupardus PJ, Maxey RJ, Murray JM, Pulk R, Rodriguez M, Savage S, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward SI, Xiao L, Xiao Y J Med Chem. 2012 Jun 28. PMID:22698084<ref>PMID:22698084</ref>

-	~~===The Jak1 kinase domain in complex with inhibitor===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22698084}}~~	+	==See Also==
-		+	*[[Janus kinase\|Janus kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4ehz~~]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHZ OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:022698084<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
-	[[Category: Lupardus, P J.]]	+	[[Category: Lupardus, P J]]
-	[[Category: Steffek, M.]]	+	[[Category: Steffek, M]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 12:06, 23 January 2013

OCA — Wed, 23 Jan 2013 12:06:11 GMT

←Older revision		Revision as of 12:06, 23 January 2013
Line 17:		Line 17:
	[[Category: Steffek, M.]]		[[Category: Steffek, M.]]
	[[Category: Kinase]]		[[Category: Kinase]]
-	[[Category: Transferase-inhibitor complex]]	+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:38, 29 August 2012

OCA — Wed, 29 Aug 2012 05:38:07 GMT

←Older revision		Revision as of 05:38, 29 August 2012
Line 1:		Line 1:
-	[[Image:4ehz.~~jpg~~\|left\|200px]]	+	[[Image:4ehz.png\|left\|200px]]

	{{STRUCTURE_4ehz\| PDB=4ehz \| SCENE= }}		{{STRUCTURE_4ehz\| PDB=4ehz \| SCENE= }}

OCA at 07:38, 4 July 2012

OCA — Wed, 04 Jul 2012 07:38:10 GMT

←Older revision		Revision as of 07:38, 4 July 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4ehz.jpg\|left\|200px]]

-	~~The entry~~ 4ehz ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4ehz\| PDB=4ehz \| SCENE= }}

-	~~Authors: Lupardus, P.J., Steffek, M.~~	+	===The Jak1 kinase domain in complex with inhibitor===

-	~~Description~~: ~~The Jak1~~ kinase ~~domain in complex with~~ inhibitor	+	{{ABSTRACT_PUBMED_22698084}}
		+
		+	==About this Structure==
		+	[[4ehz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHZ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022698084</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Lupardus, P J.]]
		+	[[Category: Steffek, M.]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase-inhibitor complex]]

OCA at 05:26, 30 May 2012

OCA — Wed, 30 May 2012 05:26:29 GMT

←Older revision		Revision as of 05:26, 30 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ehz is ON HOLD	+	The entry 4ehz is ON HOLD until Paper Publication

	Authors: Lupardus, P.J., Steffek, M.		Authors: Lupardus, P.J., Steffek, M.

	Description: The Jak1 kinase domain in complex with inhibitor		Description: The Jak1 kinase domain in complex with inhibitor

OCA: Protected "4ehz" [edit=sysop:move=sysop]

OCA — Wed, 11 Apr 2012 06:43:49 GMT

Protected "4ehz" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:43, 11 April 2012

OCA: New page: '''Unreleased structure''' The entry 4ehz is ON HOLD Authors: Lupardus, P.J., Steffek, M. Description: The Jak1 kinase domain in complex with inhibitor

OCA — Wed, 11 Apr 2012 06:43:48 GMT

New page: '''Unreleased structure''' The entry 4ehz is ON HOLD Authors: Lupardus, P.J., Steffek, M. Description: The Jak1 kinase domain in complex with inhibitor

New page

'''Unreleased structure'''

The entry 4ehz is ON HOLD

Authors: Lupardus, P.J., Steffek, M.

Description: The Jak1 kinase domain in complex with inhibitor