3qcs - Revision history

OCA at 06:02, 8 June 2022

2022-06-08T06:02:28Z

←Older revision		Revision as of 06:02, 8 June 2022
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	==Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine==		==Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine==
-	<StructureSection load='3qcs' size='340' side='right' caption='[[3qcs]], [[Resolution\|resolution]] 2.49Å' scene=''>	+	<StructureSection load='3qcs' size='340' side='right'caption='[[3qcs]], [[Resolution\|resolution]] 2.49Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qcs]] 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=3QCS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3QCS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qcs]] 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=3QCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QCS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Q1:6-[2-AMINO-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-YL]-2H-INDAZOL-3-AMINE'>3Q1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3Q1:6-[2-AMINO-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-YL]-2H-INDAZOL-3-AMINE'>3Q1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nun\|3nun]], [[3nus\|3nus]], [[3nuu\|3nuu]], [[3nuy\|3nuy]], [[3qcq\|3qcq]], [[3qcx\|3qcx]], [[3qcy\|3qcy]], [[3qd0\|3qd0]], [[3qd3\|3qd3]], [[3qd4\|3qd4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nun\|3nun]], [[3nus\|3nus]], [[3nuu\|3nuu]], [[3nuy\|3nuy]], [[3qcq\|3qcq]], [[3qcx\|3qcx]], [[3qcy\|3qcy]], [[3qd0\|3qd0]], [[3qd3\|3qd3]], [[3qd4\|3qd4]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDPK1 ([~~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">PDPK1 ([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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [~~http~~://pdbe.org/3qcs PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3qcs PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3qcs 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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [https://pdbe.org/3qcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [https://www.ebi.ac.uk/pdbsum/3qcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qcs ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>	+	[[https://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 3qcs" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3qcs" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pdk1 3D structures\|Pdk1 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Axten, J M]]		[[Category: Axten, J M]]

OCA at 09:13, 8 November 2017

2017-11-08T09:13:21Z

←Older revision		Revision as of 09:13, 8 November 2017
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 3qcs" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3qcs" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[3-phosphoinositide-dependent protein kinase 1\|3-phosphoinositide-dependent protein kinase 1]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:53, 5 August 2016

2016-08-05T08:53:40Z

←Older revision		Revision as of 08:53, 5 August 2016
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		+
	==Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine==		==Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine==
	<StructureSection load='3qcs' size='340' side='right' caption='[[3qcs]], [[Resolution\|resolution]] 2.49Å' scene=''>		<StructureSection load='3qcs' size='340' side='right' caption='[[3qcs]], [[Resolution\|resolution]] 2.49Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qcs]] 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=3QCS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QCS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qcs]] 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=3QCS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QCS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Q1:6-[2-AMINO-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-YL]-2H-INDAZOL-3-AMINE'>3Q1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Q1:6-[2-AMINO-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-YL]-2H-INDAZOL-3-AMINE'>3Q1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nun\|3nun]], [[3nus\|3nus]], [[3nuu\|3nuu]], [[3nuy\|3nuy]], [[3qcq\|3qcq]], [[3qcx\|3qcx]], [[3qcy\|3qcy]], [[3qd0\|3qd0]], [[3qd3\|3qd3]], [[3qd4\|3qd4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nun\|3nun]], [[3nus\|3nus]], [[3nuu\|3nuu]], [[3nuy\|3nuy]], [[3qcq\|3qcq]], [[3qcx\|3qcx]], [[3qcy\|3qcy]], [[3qd0\|3qd0]], [[3qd3\|3qd3]], [[3qd4\|3qd4]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDPK1 ([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">PDPK1 ([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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [http://www.ebi.ac.uk/pdbsum/3qcs 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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [http://pdbe.org/3qcs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [http://www.ebi.ac.uk/pdbsum/3qcs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qcs ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	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 3qcs" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Axten, J M]]		[[Category: Axten, J M]]

OCA at 00:56, 25 December 2014

2014-12-25T00:56:41Z

←Older revision		Revision as of 00:56, 25 December 2014
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	<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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [http://www.ebi.ac.uk/pdbsum/3qcs 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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [http://www.ebi.ac.uk/pdbsum/3qcs PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:55, 19 December 2014

2014-12-19T10:55:12Z

←Older revision		Revision as of 10:55, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3qcs\| PDB=3qcs \| SCENE= }}~~	+	==Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine==
-	===Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine===	+	<StructureSection load='3qcs' size='340' side='right' caption='[[3qcs]], [[Resolution\|resolution]] 2.49Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21341675}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3qcs]] 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=3QCS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QCS FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Q1:6-[2-AMINO-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-YL]-2H-INDAZOL-3-AMINE'>3Q1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nun\|3nun]], [[3nus\|3nus]], [[3nuu\|3nuu]], [[3nuy\|3nuy]], [[3qcq\|3qcq]], [[3qcx\|3qcx]], [[3qcy\|3qcy]], [[3qd0\|3qd0]], [[3qd3\|3qd3]], [[3qd4\|3qd4]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDPK1 ([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_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=3qcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qcs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qcs RCSB], [http://www.ebi.ac.uk/pdbsum/3qcs PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

-	~~==Function==~~	+	Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors.,Medina JR, Becker CJ, Blackledge CW, Duquenne C, Feng Y, Grant SW, Heerding D, Li WH, Miller WH, Romeril SP, Scherzer D, Shu A, Bobko MA, Chadderton AR, Dumble M, Gardiner CM, Gilbert S, Liu Q, Rabindran SK, Sudakin V, Xiang H, Brady PG, Campobasso N, Ward P, Axten JM J Med Chem. 2011 Feb 22. PMID:21341675<ref>PMID:21341675</ref>
-	~~[[http://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating~~ and ~~activating a subgroup of the AGC family of protein kinases~~. ~~Its targets include: protein kinase B (PKB/AKT1~~, ~~PKB/AKT2~~, ~~PKB/AKT3)~~, ~~p70 ribosomal protein S6 kinase (RPS6KB1)~~, ~~p90 ribosomal protein S6 kinase (RPS6KA1~~, ~~RPS6KA2 and RPS6KA3)~~, ~~cyclic AMP-dependent protein kinase (PRKACA)~~, ~~protein kinase C (PRKCD and PRKCZ)~~, ~~serum and glucocorticoid-inducible kinase (SGK1~~, ~~SGK2 and SGK3)~~, ~~p21-activated kinase-1 (PAK1)~~, ~~protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1~~, ~~thus propagating the signal to downstream targets controlling cell proliferation and survival~~, ~~as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor~~, ~~phosphorylating SMAD2~~, ~~SMAD3~~, ~~SMAD4 and SMAD7~~, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, ~~survival~~, ~~and growth of developing pancreatic cells~~. ~~Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells~~. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:~~18835241~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3qcs]] 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=3QCS OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[3-phosphoinositide-dependent protein kinase 1\|3-phosphoinositide-dependent protein kinase 1]]		*[[3-phosphoinositide-dependent protein kinase 1\|3-phosphoinositide-dependent protein kinase 1]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:021341675</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Axten, J M.]]	+	[[Category: Axten, J M]]
-	[[Category: Becker, C J.]]	+	[[Category: Becker, C J]]
-	[[Category: Blackledge, C W.]]	+	[[Category: Blackledge, C W]]
-	[[Category: Bobko, M A.]]	+	[[Category: Bobko, M A]]
-	[[Category: Brady, P G.]]	+	[[Category: Brady, P G]]
-	[[Category: Campobasso, N.]]	+	[[Category: Campobasso, N]]
-	[[Category: Chadderton, A R.]]	+	[[Category: Chadderton, A R]]
-	[[Category: Dumble, M.]]	+	[[Category: Dumble, M]]
-	[[Category: Duquenne, C.]]	+	[[Category: Duquenne, C]]
-	[[Category: Feng, Y.]]	+	[[Category: Feng, Y]]
-	[[Category: Gilbert, S.]]	+	[[Category: Gilbert, S]]
-	[[Category: Gradiner, C M.]]	+	[[Category: Gradiner, C M]]
-	[[Category: Grant, S W.]]	+	[[Category: Grant, S W]]
-	[[Category: Heerding, D.]]	+	[[Category: Heerding, D]]
-	[[Category: Li, W H.]]	+	[[Category: Li, W H]]
-	[[Category: Liu, Q.]]	+	[[Category: Liu, Q]]
-	[[Category: Medina, J R.]]	+	[[Category: Medina, J R]]
-	[[Category: Miller, W H.]]	+	[[Category: Miller, W H]]
-	[[Category: Rabindran, S K.]]	+	[[Category: Rabindran, S K]]
-	[[Category: Romeril, S P.]]	+	[[Category: Romeril, S P]]
-	[[Category: Scherzer, D.]]	+	[[Category: Scherzer, D]]
-	[[Category: Shu, A.]]	+	[[Category: Shu, A]]
-	[[Category: Sudakin, V.]]	+	[[Category: Sudakin, V]]
-	[[Category: Ward, P.]]	+	[[Category: Ward, P]]
-	[[Category: Xiang, H.]]	+	[[Category: Xiang, H]]
	[[Category: Agc kinase]]		[[Category: Agc kinase]]
	[[Category: Atp & phosphoinositide]]		[[Category: Atp & phosphoinositide]]

OCA at 08:21, 8 May 2013

2013-05-08T08:21:01Z

←Older revision		Revision as of 08:21, 8 May 2013
Line 1:		Line 1:
-	[[Image:3qcs.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3qcs", 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_3qcs\| PDB=3qcs \| SCENE= }}		{{STRUCTURE_3qcs\| PDB=3qcs \| SCENE= }}
-
	===Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine===		===Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine===
		+	{{ABSTRACT_PUBMED_21341675}}

-		+	==Function==
-	<!--	+	[[http://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN]] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
-	~~The line below this paragraph~~, ~~{{ABSTRACT_PUBMED_21341675}}~~, ~~adds~~ the ~~Publication Abstract~~ to the ~~page~~	+
-	(as ~~it appears on PubMed at http~~:~~//www~~.~~pubmed~~.~~gov)~~, ~~where 21341675~~ is the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21341675}}~~	+

	==About this Structure==		==About this Structure==
	[[3qcs]] 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=3QCS OCA].		[[3qcs]] 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=3QCS OCA].
		+
		+	==See Also==
		+	*[[3-phosphoinositide-dependent protein kinase 1\|3-phosphoinositide-dependent protein kinase 1]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21341675~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021341675</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 50:		Line 41:
	[[Category: Ward, P.]]		[[Category: Ward, P.]]
	[[Category: Xiang, H.]]		[[Category: Xiang, H.]]
		+	[[Category: Agc kinase]]
		+	[[Category: Atp & phosphoinositide]]
		+	[[Category: Phosphorylation on s241]]
		+	[[Category: Signal transduction]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:33, 30 March 2011

2011-03-30T07:33:12Z

←Older revision		Revision as of 07:33, 30 March 2011
Line 1:		Line 1:
-	[[Image:3qcs.~~jpg~~\|left\|200px]]	+	[[Image:3qcs.png\|left\|200px]]

	<!--		<!--

OCA at 06:28, 9 March 2011

2011-03-09T06:28:08Z

←Older revision		Revision as of 06:28, 9 March 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3qcs.jpg\|left\|200px]]

-	The ~~entry 3qcs~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3qcs", 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_3qcs\| PDB=3qcs \| SCENE= }}

-	Authors: Medina, J.R., Becker, C.J., Blackledge, C.W., Duquenne, C., Feng, Y., Grant, S.W., Heerding, D., Li, W.H., Miller, W.H., Romeril, S.P., Scherzer, D., Shu, A., Bobko, M.A., Chadderton, A.R., Dumble, M., Gradiner, C.M., Gilbert, S., Liu, Q., Rabindran, S.K., Sudakin, V., Xiang, H., Brady, P.G., Campobasso, N., Ward, P., Axten, J.M.	+	===Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine===

-	~~Description: Phosphoinositide~~-~~Dependent Kinase~~-1 (~~PDK1~~) ~~kinase domain with 6~~-[2-~~Amino~~-~~6-(4-morpholinyl)-4-pyrimidinyl~~]-~~1H-indazol-3-amine~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21341675}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21341675 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21341675}}
		+
		+	==About this Structure==
		+	[[3qcs]] 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=3QCS OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:21341675</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Axten, J M.]]
		+	[[Category: Becker, C J.]]
		+	[[Category: Blackledge, C W.]]
		+	[[Category: Bobko, M A.]]
		+	[[Category: Brady, P G.]]
		+	[[Category: Campobasso, N.]]
		+	[[Category: Chadderton, A R.]]
		+	[[Category: Dumble, M.]]
		+	[[Category: Duquenne, C.]]
		+	[[Category: Feng, Y.]]
		+	[[Category: Gilbert, S.]]
		+	[[Category: Gradiner, C M.]]
		+	[[Category: Grant, S W.]]
		+	[[Category: Heerding, D.]]
		+	[[Category: Li, W H.]]
		+	[[Category: Liu, Q.]]
		+	[[Category: Medina, J R.]]
		+	[[Category: Miller, W H.]]
		+	[[Category: Rabindran, S K.]]
		+	[[Category: Romeril, S P.]]
		+	[[Category: Scherzer, D.]]
		+	[[Category: Shu, A.]]
		+	[[Category: Sudakin, V.]]
		+	[[Category: Ward, P.]]
		+	[[Category: Xiang, H.]]

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

2011-01-26T12:46:17Z

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

←Older revision

Revision as of 12:46, 26 January 2011

OCA: New page: '''Unreleased structure''' The entry 3qcs is ON HOLD Authors: Medina, J.R., Becker, C.J., Blackledge, C.W., Duquenne, C., Feng, Y., Grant, S.W., Heerding, D., Li, W.H., Miller, W.H., Ro...

2011-01-26T12:46:17Z

New page: '''Unreleased structure''' The entry 3qcs is ON HOLD Authors: Medina, J.R., Becker, C.J., Blackledge, C.W., Duquenne, C., Feng, Y., Grant, S.W., Heerding, D., Li, W.H., Miller, W.H., Ro...

New page

'''Unreleased structure'''

The entry 3qcs is ON HOLD

Authors: Medina, J.R., Becker, C.J., Blackledge, C.W., Duquenne, C., Feng, Y., Grant, S.W., Heerding, D., Li, W.H., Miller, W.H., Romeril, S.P., Scherzer, D., Shu, A., Bobko, M.A., Chadderton, A.R., Dumble, M., Gradiner, C.M., Gilbert, S., Liu, Q., Rabindran, S.K., Sudakin, V., Xiang, H., Brady, P.G., Campobasso, N., Ward, P., Axten, J.M.

Description: Phosphoinositide-Dependent Kinase-1 (PDK1) kinase domain with 6-[2-Amino-6-(4-morpholinyl)-4-pyrimidinyl]-1H-indazol-3-amine