7r9t - Revision history

OCA at 16:27, 18 October 2023

OCA — Wed, 18 Oct 2023 16:27:41 GMT

←Older revision		Revision as of 16:27, 18 October 2023
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	<StructureSection load='7r9t' size='340' side='right'caption='[[7r9t]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='7r9t' size='340' side='right'caption='[[7r9t]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7r9t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R9T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7r9t]] 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=7R9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R9T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TR:6-amino-3-[(1S,3R)-4-chloro-3-hydroxy-1,2-dihydrospiro[cyclopentane-1,3-pyrrolo[2,3-b]pyridin]-5-yl]-2-fluoro-N,N-dimethylbenzamide'>2TR</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]] 2Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TR:6-amino-3-[(1S,3R)-4-chloro-3-hydroxy-1,2-dihydrospiro[cyclopentane-1,3-pyrrolo[2,3-b]pyridin]-5-yl]-2-fluoro-N,N-dimethylbenzamide'>2TR</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=7r9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r9t OCA], [https://pdbe.org/7r9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r9t RCSB], [https://www.ebi.ac.uk/pdbsum/7r9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r9t 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=7r9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r9t OCA], [https://pdbe.org/7r9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r9t RCSB], [https://www.ebi.ac.uk/pdbsum/7r9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r9t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN]] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>	+	[https://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Lehoux I]]
-	[[Category: Lehoux, I]]	+	[[Category: Wang W]]
-	[[Category: Wang, W]]	+	[[Category: Wu P]]
-	[[Category: Wu, P]]	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Map4k1]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:37, 9 February 2022

OCA — Wed, 09 Feb 2022 07:37:17 GMT

←Older revision		Revision as of 07:37, 9 February 2022
Line 1:		Line 1:

	==Crystal structure of HPK1 in complex with compound 17==		==Crystal structure of HPK1 in complex with compound 17==
-	<StructureSection load='7r9t' size='340' side='right'caption='[[7r9t]]' scene=''>	+	<StructureSection load='7r9t' size='340' side='right'caption='[[7r9t]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R9T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7r9t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R9T FirstGlance]. <br>
-	</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=7r9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r9t OCA], [https://pdbe.org/7r9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r9t RCSB], [https://www.ebi.ac.uk/pdbsum/7r9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r9t ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TR:6-amino-3-[(1S,3R)-4-chloro-3-hydroxy-1,2-dihydrospiro[cyclopentane-1,3-pyrrolo[2,3-b]pyridin]-5-yl]-2-fluoro-N,N-dimethylbenzamide'>2TR</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7r9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r9t OCA], [https://pdbe.org/7r9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r9t RCSB], [https://www.ebi.ac.uk/pdbsum/7r9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r9t ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN]] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hematopoietic progenitor kinase 1 (HPK1) is implicated as a negative regulator of T-cell receptor-induced T-cell activation. Studies using HPK1 kinase-dead knock-in animals have demonstrated the loss of HPK1 kinase activity resulted in an increase in T-cell function and tumor growth inhibition in glioma models. Herein, we describe the discovery of a series of small molecule inhibitors of HPK1. Using a structure-based drug design approach, the kinase selectivity of the molecules was significantly improved by inducing and stabilizing an unusual P-loop folded binding mode. The metabolic liabilities of the initial 7-azaindole high-throughput screening hit were mitigated by addressing a key metabolic soft spot along with physicochemical property-based optimization. The resulting spiro-azaindoline HPK1 inhibitors demonstrated improved in vitro ADME properties and the ability to induce cytokine production in primary human T-cells.
		+
		+	Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).,Chan BK, Seward E, Lainchbury M, Brewer TF, An L, Blench T, Cartwright MW, Chan GKY, Choo EF, Drummond J, Elliott RL, Gancia E, Gazzard L, Hu B, Jones GE, Luo X, Madin A, Malhotra S, Moffat JG, Pang J, Salphati L, Sneeringer CJ, Stivala CE, Wei B, Wang W, Wu P, Heffron TP ACS Med Chem Lett. 2021 Dec 8;13(1):84-91. doi: 10.1021/acsmedchemlett.1c00473., eCollection 2022 Jan 13. PMID:35059127<ref>PMID:35059127</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7r9t" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lehoux I]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Wang W]]	+	[[Category: Lehoux, I]]
-	[[Category: Wu P]]	+	[[Category: Wang, W]]
		+	[[Category: Wu, P]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Map4k1]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:40, 5 January 2022

OCA — Wed, 05 Jan 2022 10:40:51 GMT

←Older revision		Revision as of 10:40, 5 January 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7r9t ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of HPK1 in complex with compound 17==
-		+	<StructureSection load='7r9t' size='340' side='right'caption='[[7r9t]]' scene=''>
-	~~Authors~~: Wu, P., ~~Lehoux~~, I., ~~Wang~~, W.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R9T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R9T FirstGlance]. <br>
-	~~Description: Crystal structure of HPK1 in complex with compound 17~~	+	</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=7r9t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r9t OCA], [https://pdbe.org/7r9t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r9t RCSB], [https://www.ebi.ac.uk/pdbsum/7r9t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r9t ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Wang, W~~]]	+	__TOC__
-	[[Category: ~~Wu, P~~]]	+	</StructureSection>
-	[[Category: ~~Lehoux, I~~]]	+	[[Category: Large Structures]]
		+	[[Category: Lehoux I]]
		+	[[Category: Wang W]]
		+	[[Category: Wu P]]

OCA at 09:18, 4 August 2021

OCA — Wed, 04 Aug 2021 09:18:29 GMT

←Older revision		Revision as of 09:18, 4 August 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7r9t is ON HOLD	+	The entry 7r9t is ON HOLD until Paper Publication

	Authors: Wu, P., Lehoux, I., Wang, W.		Authors: Wu, P., Lehoux, I., Wang, W.

OCA: Protected "7r9t" [edit=sysop:move=sysop]

OCA — Wed, 07 Jul 2021 09:00:47 GMT

Protected "7r9t" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:00, 7 July 2021

OCA: New page: '''Unreleased structure''' The entry 7r9t is ON HOLD Authors: Wu, P., Lehoux, I., Wang, W. Description: Crystal structure of HPK1 in complex with compound 17 [[Category: Unreleased Str...

OCA — Wed, 07 Jul 2021 09:00:46 GMT

New page: '''Unreleased structure''' The entry 7r9t is ON HOLD Authors: Wu, P., Lehoux, I., Wang, W. Description: Crystal structure of HPK1 in complex with compound 17 [[Category: Unreleased Str...

New page

'''Unreleased structure'''

The entry 7r9t is ON HOLD

Authors: Wu, P., Lehoux, I., Wang, W.

Description: Crystal structure of HPK1 in complex with compound 17
[[Category: Unreleased Structures]]
[[Category: Wang, W]]
[[Category: Wu, P]]
[[Category: Lehoux, I]]