3vap - Revision history

OCA at 10:34, 1 March 2024

OCA — Fri, 01 Mar 2024 10:34:36 GMT

←Older revision		Revision as of 10:34, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='3vap' size='340' side='right'caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>		<StructureSection load='3vap' size='340' side='right'caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vap]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VAP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vap]] 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VAP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</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]] 2.66Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [https://pdbe.org/3vap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [https://www.ebi.ac.uk/pdbsum/3vap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vap 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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [https://pdbe.org/3vap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [https://www.ebi.ac.uk/pdbsum/3vap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vap ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>	+	[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied. Additionally, several of the more potent inhibitors were screened for their off-target kinase selectivity.	+
-		+
-	Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.,Voss ME, Rainka MP, Fleming M, Peterson LH, Belanger DB, Siddiqui MA, Hruza A, Voigt J, Gray K, Basso AD Bioorg Med Chem Lett. 2012 Mar 21. PMID:22503250<ref>PMID:22503250</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3vap" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Basso AD]]
-	[[Category: Basso~~, A D~~]]	+	[[Category: Belanger DB]]
-	[[Category: Belanger~~, D B~~]]	+	[[Category: Fleming M]]
-	[[Category: Fleming, M]]	+	[[Category: Gray K]]
-	[[Category: Gray, K]]	+	[[Category: Hruza A]]
-	[[Category: Hruza, A]]	+	[[Category: Peterson LH]]
-	[[Category: Peterson~~, L H~~]]	+	[[Category: Rainka MP]]
-	[[Category: Rainka~~, M P~~]]	+	[[Category: Siddiqui MA]]
-	[[Category: Siddiqui~~, M A~~]]	+	[[Category: Voigt J]]
-	[[Category: Voigt, J]]	+	[[Category: Voss ME]]
-	[[Category: Voss~~, M E]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 18:35, 27 July 2022

OCA — Wed, 27 Jul 2022 18:35:36 GMT

←Older revision		Revision as of 18:35, 27 July 2022
Line 1:		Line 1:

	==Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity==		==Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity==
-	<StructureSection load='3vap' size='340' side='right' caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>	+	<StructureSection load='3vap' size='340' side='right'caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vap]] 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VAP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vap]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VAP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([https://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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [~~http~~://pdbe.org/3vap PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vap PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vap 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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [https://pdbe.org/3vap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [https://www.ebi.ac.uk/pdbsum/3vap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vap ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>	+	[[https://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Basso, A D]]		[[Category: Basso, A D]]

OCA at 12:09, 5 August 2016

OCA — Fri, 05 Aug 2016 12:09:46 GMT

←Older revision		Revision as of 12:09, 5 August 2016
Line 1:		Line 1:
		+
	==Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity==		==Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity==
	<StructureSection load='3vap' size='340' side='right' caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>		<StructureSection load='3vap' size='340' side='right' caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vap]] is a 1 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vap]] 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [http://www.ebi.ac.uk/pdbsum/3vap 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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [http://pdbe.org/3vap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [http://www.ebi.ac.uk/pdbsum/3vap PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vap ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3vap" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Basso, A D]]		[[Category: Basso, A D]]

OCA at 18:43, 25 December 2014

OCA — Thu, 25 Dec 2014 18:43:16 GMT

←Older revision		Revision as of 18:43, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vap]] is a 1 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vap]] is a 1 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAP FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [http://www.ebi.ac.uk/pdbsum/3vap 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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [http://www.ebi.ac.uk/pdbsum/3vap PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Basso, A D.]]	+	[[Category: Basso, A D]]
-	[[Category: Belanger, D B.]]	+	[[Category: Belanger, D B]]
-	[[Category: Fleming, M.]]	+	[[Category: Fleming, M]]
-	[[Category: Gray, K.]]	+	[[Category: Gray, K]]
-	[[Category: Hruza, A.]]	+	[[Category: Hruza, A]]
-	[[Category: Peterson, L H.]]	+	[[Category: Peterson, L H]]
-	[[Category: Rainka, M P.]]	+	[[Category: Rainka, M P]]
-	[[Category: Siddiqui, M A.]]	+	[[Category: Siddiqui, M A]]
-	[[Category: Voigt, J.]]	+	[[Category: Voigt, J]]
-	[[Category: Voss, M E.]]	+	[[Category: Voss, M E]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]

OCA at 07:36, 5 June 2014

OCA — Thu, 05 Jun 2014 07:36:25 GMT

←Older revision		Revision as of 07:36, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3vap.~~png~~\|~~left~~\|~~200px~~]]	+	==Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity==
		+	<StructureSection load='3vap' size='340' side='right' caption='[[3vap]], [[Resolution\|resolution]] 2.66Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3vap]] is a 1 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=3VAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VAP FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0FY:3-(1-{2-[(3-FLUOROPYRIDINIUM-4-YL)AMINO]-2-OXOETHYL}-1H-PYRAZOL-4-YL)-6-METHYL-8-[(3-{[(1R,3R)-3-METHYLPIPERIDINIUM-1-YL]METHYL}-1,2-THIAZOL-5-YL)AMINO]IMIDAZO[1,2-A]PYRAZIN-1-IUM'>0FY</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3vap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vap OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vap RCSB], [http://www.ebi.ac.uk/pdbsum/3vap PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied. Additionally, several of the more potent inhibitors were screened for their off-target kinase selectivity.

-	<!--	+	Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.,Voss ME, Rainka MP, Fleming M, Peterson LH, Belanger DB, Siddiqui MA, Hruza A, Voigt J, Gray K, Basso AD Bioorg Med Chem Lett. 2012 Mar 21. PMID:22503250<ref>PMID:22503250</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_3vap"~~, ~~creates the "Structure Box" on the page.~~	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded)~~,	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_3vap\| PDB=3vap \| SCENE= }}~~	+

-	~~===Synthesis and SAR Studies of imidazo-[1~~,2-a~~]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-		+	==See Also==
-	~~<!--~~	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22503250}}, adds the Publication Abstract to the page~~	+	== References ==
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 22503250 is the PubMed ID number.~~	+	<references/>
-	~~-->~~	+	__TOC__
-	~~{{ABSTRACT_PUBMED_22503250}}~~	+	</StructureSection>
-		+
-	==~~About this Structure~~==	+
-	[[~~3vap]] is a 1 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=3VAP OCA~~].	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022503250<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 05:06, 23 May 2012

OCA — Wed, 23 May 2012 05:06:55 GMT

←Older revision		Revision as of 05:06, 23 May 2012
Line 1:		Line 1:
-	[[Image:3vap.~~jpg~~\|left\|200px]]	+	[[Image:3vap.png\|left\|200px]]

	<!--		<!--

OCA at 19:17, 2 May 2012

OCA — Wed, 02 May 2012 19:17:23 GMT

←Older revision		Revision as of 19:17, 2 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3vap.jpg\|left\|200px]]

-	The ~~entry 3vap~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3vap", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3vap\| PDB=3vap \| SCENE= }}

-	~~Authors: Voss~~, ~~M.E., Rainka, M.P., Fleming, M., Peterson, L.H., Belanger, D.B., Siddiqui, M.A., Hruza, A., Voigt, J., Basso, A.D., Gray, K.~~	+	===Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity===

-	~~Description~~: ~~Synthesis and SAR Studies of imidazo~~-[1,2-a]-~~pyrazine Aurora~~ kinase ~~inhibitors with improved off target kinase selectivity~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22503250}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22503250 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22503250}}
		+
		+	==About this Structure==
		+	[[3vap]] is a 1 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=3VAP OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022503250</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Basso, A D.]]
		+	[[Category: Belanger, D B.]]
		+	[[Category: Fleming, M.]]
		+	[[Category: Gray, K.]]
		+	[[Category: Hruza, A.]]
		+	[[Category: Peterson, L H.]]
		+	[[Category: Rainka, M P.]]
		+	[[Category: Siddiqui, M A.]]
		+	[[Category: Voigt, J.]]
		+	[[Category: Voss, M E.]]
		+	[[Category: Cell cycle]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:52, 1 February 2012

OCA — Wed, 01 Feb 2012 06:52:12 GMT

←Older revision		Revision as of 06:52, 1 February 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3vap is ON HOLD	+	The entry 3vap is ON HOLD until Paper Publication

	Authors: Voss, M.E., Rainka, M.P., Fleming, M., Peterson, L.H., Belanger, D.B., Siddiqui, M.A., Hruza, A., Voigt, J., Basso, A.D., Gray, K.		Authors: Voss, M.E., Rainka, M.P., Fleming, M., Peterson, L.H., Belanger, D.B., Siddiqui, M.A., Hruza, A., Voigt, J., Basso, A.D., Gray, K.

	Description: Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity		Description: Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity

OCA at 05:59, 11 January 2012

OCA — Wed, 11 Jan 2012 05:59:46 GMT

←Older revision		Revision as of 05:59, 11 January 2012
Line 3:		Line 3:
	The entry 3vap is ON HOLD		The entry 3vap is ON HOLD

-	Authors: Voss, M. E., Rainka, M. P., Fleming, M., Peterson, L. H., Belanger, D. B., Siddiqui, M. A., Hruza, A., Voigt, J., Basso, A. D., Gray, K.	+	Authors: Voss, M.E., Rainka, M.P., Fleming, M., Peterson, L.H., Belanger, D.B., Siddiqui, M.A., Hruza, A., Voigt, J., Basso, A.D., Gray, K.

	Description: Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity		Description: Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity

OCA: Protected "3vap" [edit=sysop:move=sysop]

OCA — Wed, 04 Jan 2012 05:48:30 GMT

Protected "3vap" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:48, 4 January 2012