4e4n - Revision history

OCA at 09:57, 30 October 2024

2024-10-30T09:57:16Z

← Older revision		Revision as of 09:57, 30 October 2024
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	== Function ==		== Function ==
	[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.		[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;">
			== Publication Abstract from PubMed ==
			A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino analogs demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of sub-nanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogs to enhance affinity and selectivity.

			Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4e4n" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Janus kinase 3D structures\|Janus kinase 3D structures]]		*[[Janus kinase 3D structures\|Janus kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 14:52, 14 March 2024

2024-03-14T14:52:31Z

← Older revision		Revision as of 14:52, 14 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[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.		[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;">~~
	~~== Publication Abstract from PubMed ==~~
	A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino analogs demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of sub-nanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogs to enhance affinity and selectivity.

	~~Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>~~

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e4n" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Janus kinase 3D structures\|Janus kinase 3D structures]]		*[[Janus kinase 3D structures\|Janus kinase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:21, 6 December 2023

2023-12-06T08:21:16Z

← Older revision		Revision as of 08:21, 6 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4N FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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]] 1.9Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene>, <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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [https://pdbe.org/4e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [https://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n 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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [https://pdbe.org/4e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [https://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[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.		[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 ==

OCA at 06:49, 28 September 2022

2022-09-28T06:49:43Z

← Older revision		Revision as of 06:49, 28 September 2022
Line 1:		Line 1:

	==JAK1 kinase (JH1 domain) in complex with compound 49==		==JAK1 kinase (JH1 domain) in complex with compound 49==
	<StructureSection load='4e4n' size='340' side='right' caption='[[4e4n]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4e4n' size='340' side='right'caption='[[4e4n]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E4N FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [https://pdbe.org/4e4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [https://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n ProSAT]</span></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [~~http~~://pdbe.org/4e4n PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n 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 24:		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: Eigenbrot, C]]		[[Category: Eigenbrot C]]
	~~[[Category: O-phosphotyrosine]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 13:01, 5 August 2016

2016-08-05T13:01:39Z

← Older revision		Revision as of 13:01, 5 August 2016
Line 1:		Line 1:

	==JAK1 kinase (JH1 domain) in complex with compound 49==		==JAK1 kinase (JH1 domain) in complex with compound 49==
	<StructureSection load='4e4n' size='340' side='right' caption='[[4e4n]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4e4n' size='340' side='right' caption='[[4e4n]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4n]] is a 2 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4N FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4n]] 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [http://www.ebi.ac.uk/pdbsum/4e4n 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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [http://pdbe.org/4e4n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [http://www.ebi.ac.uk/pdbsum/4e4n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4n ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	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 4e4n" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]
	[[Category: O-phosphotyrosine]]		[[Category: O-phosphotyrosine]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 19:03, 25 December 2014

2014-12-25T19:03:23Z

← Older revision		Revision as of 19:03, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4n]] is a 2 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4N FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4n]] is a 2 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene></td></tr>
	<tr><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><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</td></tr>
	<tr><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 Homo sapiens])</td></tr>
	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [http://www.ebi.ac.uk/pdbsum/4e4n 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=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [http://www.ebi.ac.uk/pdbsum/4e4n PDBsum]</span></td></tr>
	<table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 16:		Line 18:
	Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>		Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>

	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>

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	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Eigenbrot, C.]]		[[Category: Eigenbrot, C]]
	[[Category: O-phosphotyrosine]]		[[Category: O-phosphotyrosine]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:17, 5 June 2014

2014-06-05T07:17:32Z

← Older revision		Revision as of 07:17, 5 June 2014
Line 1:		Line 1:
	[[~~Image~~:~~4e4n~~.~~png~~\|~~left~~\|~~200px~~]]		==JAK1 kinase (JH1 domain) in complex with compound 49==
			<StructureSection load='4e4n' size='340' side='right' caption='[[4e4n]], [[Resolution\|resolution]] 1.90Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4e4n]] is a 2 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=4E4N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4N FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NL:TERT-BUTYL+[(1R,3R)-3-(IMIDAZO[4,5-D]PYRROLO[2,3-B]PYRIDIN-1(6H)-YL)CYCLOPENTYL]CARBAMATE'>0NL</scene><br>
			<tr><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><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e4l\|4e4l]], [[4e4m\|4e4m]], [[4e5w\|4e5w]], [[4e6d\|4e6d]], [[4e6q\|4e6q]]</td></tr>
			<tr><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><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4n RCSB], [http://www.ebi.ac.uk/pdbsum/4e4n PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino analogs demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of sub-nanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogs to enhance affinity and selectivity.

	~~{{STRUCTURE_4e4n\| PDB=4e4n \| SCENE= }}~~		Identification of Imidazo-pyrrolopyridines as Novel and Potent JAK1 Inhibitors.,Kulagowski J J Med Chem. 2012 May 16. PMID:22591402<ref>PMID:22591402</ref>

	~~===JAK1 kinase (JH1 domain) in complex with compound 49===~~		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_22591402}}~~		==See Also==
			*[[Janus kinase\|Janus kinase]]
	==~~About this Structure~~==		== References ==
	[[~~4e4n]] is a 2 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=4E4N OCA~~].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:022591402<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 07:27, 11 July 2012

2012-07-11T07:27:53Z

← Older revision		Revision as of 07:27, 11 July 2012
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	[[Image:4e4n.~~jpg~~\|left\|200px]]		[[Image:4e4n.png\|left\|200px]]

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	{{STRUCTURE_4e4n\| PDB=4e4n \| SCENE= }}		{{STRUCTURE_4e4n\| PDB=4e4n \| SCENE= }}

	===JAK1 kinase (JH1 domain) in complex with compound 49===		===JAK1 kinase (JH1 domain) in complex with compound 49===


	~~<!--~~
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OCA at 05:51, 30 May 2012

2012-05-30T05:51:41Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4e4n.jpg|left|200px]]
-The entry 4e4n is ON HOLD  until Paper Publication
+<!--
-Authors: Eigenbrot, C.
+===JAK1 kinase (JH1 domain) in complex with compound 49===
-Description: Kinase/inhibitor

OCA at 05:45, 4 April 2012

2012-04-04T05:45:09Z

← Older revision		Revision as of 05:45, 4 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e4n is ON HOLD		The entry 4e4n is ON HOLD until Paper Publication

	Authors: Eigenbrot, C.		Authors: Eigenbrot, C.

	Description: Kinase/inhibitor		Description: Kinase/inhibitor