5u6i - Revision history

OCA at 13:21, 4 October 2023

2023-10-04T13:21:50Z

←Older revision		Revision as of 13:21, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5u6i' size='340' side='right'caption='[[5u6i]], [[Resolution\|resolution]] 1.69Å' scene=''>		<StructureSection load='5u6i' size='340' side='right'caption='[[5u6i]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5U6I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u6i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U6I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81Y:3-[2-(MORPHOLIN-4-YL)PYRIDIN-4-YL]-5-[(PROPAN-2-YL)OXY]-1H-INDAZOLE'>81Y</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.69Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81Y:3-[2-(MORPHOLIN-4-YL)PYRIDIN-4-YL]-5-[(PROPAN-2-YL)OXY]-1H-INDAZOLE'>81Y</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5u6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6i OCA], [~~http~~://pdbe.org/5u6i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u6i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u6i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6i 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=5u6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6i OCA], [https://pdbe.org/5u6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u6i RCSB], [https://www.ebi.ac.uk/pdbsum/5u6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MK01_RAT MK01_RAT]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:21070949</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity (By similarity).<ref>PMID:21070949</ref>	+	[https://www.uniprot.org/uniprot/MK01_RAT MK01_RAT] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:21070949</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity (By similarity).<ref>PMID:21070949</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mitogen-activated protein kinase~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: Agnihotri, G]]	+	[[Category: Agnihotri G]]
-	[[Category: Baptista, M]]	+	[[Category: Baptista M]]
-	[[Category: Basu, K]]	+	[[Category: Basu K]]
-	[[Category: Chang~~, R K~~]]	+	[[Category: Chang RK]]
-	[[Category: Columbus, J]]	+	[[Category: Columbus J]]
-	[[Category: Dai, X]]	+	[[Category: Dai X]]
-	[[Category: DeMong~~, D E~~]]	+	[[Category: DeMong DE]]
-	[[Category: Drolet~~, R E~~]]	+	[[Category: Drolet RE]]
-	[[Category: Embrey~~, M W~~]]	+	[[Category: Embrey MW]]
-	[[Category: Fell~~, M J~~]]	+	[[Category: Fell MJ]]
-	[[Category: Greshock~~, T J~~]]	+	[[Category: Greshock TJ]]
-	[[Category: Harris, J]]	+	[[Category: Harris J]]
-	[[Category: Hruza, A]]	+	[[Category: Hruza A]]
-	[[Category: Kennedy~~, M E~~]]	+	[[Category: Kennedy ME]]
-	[[Category: Kern~~, J T~~]]	+	[[Category: Kern JT]]
-	[[Category: Li, W]]	+	[[Category: Li W]]
-	[[Category: Lin, S]]	+	[[Category: Lin S]]
-	[[Category: Lin, Y]]	+	[[Category: Lin Y]]
-	[[Category: Liu, H]]	+	[[Category: Liu H]]
-	[[Category: McCauley~~, J A~~]]	+	[[Category: McCauley JA]]
-	[[Category: Mei, H]]	+	[[Category: Mei H]]
-	[[Category: Miller~~, M W~~]]	+	[[Category: Miller MW]]
-	[[Category: Mirescu, C]]	+	[[Category: Mirescu C]]
-	[[Category: Morrow~~, J A~~]]	+	[[Category: Morrow JA]]
-	[[Category: Nargund, R]]	+	[[Category: Nargund R]]
-	[[Category: Parker~~, E M~~]]	+	[[Category: Parker EM]]
-	[[Category: Poirier, M]]	+	[[Category: Poirier M]]
-	[[Category: Sanders~~, J M~~]]	+	[[Category: Sanders JM]]
-	[[Category: Scott~~, J D~~]]	+	[[Category: Scott JD]]
-	[[Category: Stamford~~, A W~~]]	+	[[Category: Stamford AW]]
-	[[Category: Tiscia~~, H E~~]]	+	[[Category: Tiscia HE]]
-	[[Category: Xiao, L]]	+	[[Category: Xiao L]]
-	[[Category: Yin, Z]]	+	[[Category: Yin Z]]
-	[[Category: Zhou, X]]	+	[[Category: Zhou X]]
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Kinase selectivity]]~~	+
-	~~[[Category: Lrrk2]]~~	+
-	~~[[Category: Map kinase]]~~	+
-	~~[[Category: Mli-2]]~~	+
-	~~[[Category: Parkinson's disease]]~~	+
-	~~[[Category: Serine/ threonine-protein kinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 12:27, 23 September 2020

2020-09-23T12:27:55Z

←Older revision		Revision as of 12:27, 23 September 2020
Line 1:		Line 1:

	==Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity==		==Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity==
-	<StructureSection load='5u6i' size='340' side='right' caption='[[5u6i]], [[Resolution\|resolution]] 1.69Å' scene=''>	+	<StructureSection load='5u6i' size='340' side='right'caption='[[5u6i]], [[Resolution\|resolution]] 1.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6I OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U6I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U6I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=81Y:3-[2-(MORPHOLIN-4-YL)PYRIDIN-4-YL]-5-[(PROPAN-2-YL)OXY]-1H-INDAZOLE'>81Y</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=81Y:3-[2-(MORPHOLIN-4-YL)PYRIDIN-4-YL]-5-[(PROPAN-2-YL)OXY]-1H-INDAZOLE'>81Y</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=5u6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6i OCA], [http://pdbe.org/5u6i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u6i RCSB], [http://www.ebi.ac.uk/pdbsum/5u6i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6i ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5u6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6i OCA], [http://pdbe.org/5u6i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u6i RCSB], [http://www.ebi.ac.uk/pdbsum/5u6i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5u6i" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5u6i" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Agnihotri, G]]		[[Category: Agnihotri, G]]

OCA at 21:12, 15 March 2017

2017-03-15T21:12:16Z

←Older revision		Revision as of 21:12, 15 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u6i is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity==
		+	<StructureSection load='5u6i' size='340' side='right' caption='[[5u6i]], [[Resolution\|resolution]] 1.69Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5u6i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U6I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=81Y:3-[2-(MORPHOLIN-4-YL)PYRIDIN-4-YL]-5-[(PROPAN-2-YL)OXY]-1H-INDAZOLE'>81Y</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=5u6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6i OCA], [http://pdbe.org/5u6i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u6i RCSB], [http://www.ebi.ac.uk/pdbsum/5u6i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6i ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MK01_RAT MK01_RAT]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:21070949</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity (By similarity).<ref>PMID:21070949</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	: Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multidomain protein which contains a kinase domain and GTPase domain among other regions. Individuals possessing gain of function mutations in the kinase domain such as the most prevalent G2019S mutation have been associated with an increased risk for the development of Parkinson's Disease (PD). Given this genetic validation for inhibition of LRRK2 kinase activity as a potential means of effecting disesase progression, our team set out to develop LRRK2 inhibitors to test this hypothesis. A high throughput screen of our compound collection afforded a number of promising indazole leads which were truncated in order to identify a minimum pharmacophore. Further optimization of these indazoles led to the development of MLi-2 (1): a potent, highly selective, orally available, brain penetrant inhibitor of LRRK2.

-	~~Authors: Scott~~, ~~J.D~~., DeMong, ~~D.E., Fell, M.J., Mirescu, C.~~, Basu, K., ~~Greshock~~, T.J., ~~Morrow, J.~~A., ~~Xiao~~, L., ~~Hruza~~, A., ~~Harris~~, ~~J., Tiscia~~, H~~.E.~~, ~~Chang, R.K., Embrey~~, M~~.W.~~, ~~McCauley~~, ~~J.A.~~, ~~Li, W., Lin, S., Liu, H., Dai, X.~~, Baptista, M., ~~Agnihotri~~, G., ~~Columbus~~, J., ~~Mei~~, H., ~~Poirier~~, M., Zhou, X., ~~Lin~~, ~~Y., Yin, Z.~~, Sanders, ~~J.M.~~, Drolet~~, R.E.~~, Kern, ~~J.T.~~, Kennedy~~, M.E.~~, Parker~~, E.M.~~, Stamford~~, A.W.~~, Nargund, R., Miller~~, M~~.W.	+	Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity.,Scott JD, DeMong DE, Greshock TJ, Basu K, Dai X, Harris J, Hruza A, Li SW, Lin SI, Liu H, Macala MK, Hu Z, Mei H, Zhang H, Walsh P, Poirier M, Shi ZC, Xiao L, Agnihotri G, Baptista MA, Columbus J, Fell MJ, Hyde LA, Kuvelkar R, Lin Y, Mirescu C, Morrow JA, Yin Z, Zhang X, Zhou X, Chang RK, Embrey MW, Sanders JM, Tiscia HE, Drolet RE, Kern JT, Sur SM, Renger JJ, Bilodeau MT, Kennedy ME, Parker EM, Stamford AW, Nargund RP, McCauley JA, Miller MW J Med Chem. 2017 Feb 28. doi: 10.1021/acs.jmedchem.7b00045. PMID:28245354<ref>PMID:28245354</ref>

-	~~Description: Discovery~~ of ~~MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Zhou, X]]~~	+	<div class="pdbe-citations 5u6i" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Nargund, R~~]]	+	== References ==
-	[[Category: ~~Demong~~, ~~D.E~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase]]
		+	[[Category: Agnihotri, G]]
	[[Category: Baptista, M]]		[[Category: Baptista, M]]
-	[[Category: Embrey, M.W]]
-	[[Category: Kennedy, M.E]]
-	[[Category: Poirier, M]]
-	[[Category: Parker, E.M]]
-	[[Category: Chang, R.K]]
-	[[Category: Xiao, L]]
	[[Category: Basu, K]]		[[Category: Basu, K]]
-	[[Category: ~~Harris~~, ~~J]]~~	+	[[Category: Chang, R K]]
-	~~[[Category: Fell, M.J]]~~	+
-	~~[[Category: Lin, S]]~~	+
-	~~[[Category: Miller, M.W]]~~	+
-	~~[[Category: Liu, H]]~~	+
-	~~[[Category: Sanders, J.M~~]]	+
	[[Category: Columbus, J]]		[[Category: Columbus, J]]
-	[[Category: ~~Morrow~~, J.A]]	+	[[Category: Dai, X]]
		+	[[Category: DeMong, D E]]
		+	[[Category: Drolet, R E]]
		+	[[Category: Embrey, M W]]
		+	[[Category: Fell, M J]]
		+	[[Category: Greshock, T J]]
		+	[[Category: Harris, J]]
	[[Category: Hruza, A]]		[[Category: Hruza, A]]
-	[[Category: ~~Stamford~~, ~~A.W]]~~	+	[[Category: Kennedy, M E]]
-	~~[[Category: Mccauley, J.A~~]]	+	[[Category: Kern, J T]]
-	[[Category: Kern, J.T]]	+
-	~~[[Category: Greshock, T.J]]~~	+
-	~~[[Category: Tiscia, H.E]]~~	+
-	~~[[Category: Yin, Z]]~~	+
-	~~[[Category: Mirescu, C~~]]	+
	[[Category: Li, W]]		[[Category: Li, W]]
		+	[[Category: Lin, S]]
	[[Category: Lin, Y]]		[[Category: Lin, Y]]
-	[[Category: ~~Scott~~, ~~J.D~~]]	+	[[Category: Liu, H]]
-	[[Category: ~~Dai~~, ~~X]]~~	+	[[Category: McCauley, J A]]
-	~~[[Category: Agnihotri, G]]~~	+
-	~~[[Category: Drolet, R.E~~]]	+
	[[Category: Mei, H]]		[[Category: Mei, H]]
		+	[[Category: Miller, M W]]
		+	[[Category: Mirescu, C]]
		+	[[Category: Morrow, J A]]
		+	[[Category: Nargund, R]]
		+	[[Category: Parker, E M]]
		+	[[Category: Poirier, M]]
		+	[[Category: Sanders, J M]]
		+	[[Category: Scott, J D]]
		+	[[Category: Stamford, A W]]
		+	[[Category: Tiscia, H E]]
		+	[[Category: Xiao, L]]
		+	[[Category: Yin, Z]]
		+	[[Category: Zhou, X]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Kinase selectivity]]
		+	[[Category: Lrrk2]]
		+	[[Category: Map kinase]]
		+	[[Category: Mli-2]]
		+	[[Category: Parkinson's disease]]
		+	[[Category: Serine/ threonine-protein kinase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 14:12, 9 March 2017

2017-03-09T14:12:39Z

←Older revision		Revision as of 14:12, 9 March 2017
Line 30:		Line 30:
	[[Category: Mccauley, J.A]]		[[Category: Mccauley, J.A]]
	[[Category: Kern, J.T]]		[[Category: Kern, J.T]]
-	[[Category: Yin, Z]]
-	[[Category: Tiscia, H.E]]
	[[Category: Greshock, T.J]]		[[Category: Greshock, T.J]]
		+	[[Category: Tiscia, H.E]]
		+	[[Category: Yin, Z]]
	[[Category: Mirescu, C]]		[[Category: Mirescu, C]]
-	[[Category: Lin, Y]]
	[[Category: Li, W]]		[[Category: Li, W]]
		+	[[Category: Lin, Y]]
	[[Category: Scott, J.D]]		[[Category: Scott, J.D]]
	[[Category: Dai, X]]		[[Category: Dai, X]]
-	[[Category: Drolet, R.E]]
	[[Category: Agnihotri, G]]		[[Category: Agnihotri, G]]
		+	[[Category: Drolet, R.E]]
	[[Category: Mei, H]]		[[Category: Mei, H]]

OCA at 20:27, 22 December 2016

2016-12-22T20:27:03Z

←Older revision		Revision as of 20:27, 22 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5u6i is ON HOLD	+	The entry 5u6i is ON HOLD until Paper Publication

-	Authors: Scott, J. D., DeMong D. E., Fell, M. J., Mirescu, C., Basu, K., Greshock, T. J., Morrow, J. A., Xiao, L., Hruza, A., Harris, J., Tiscia, H. E., Chang, R. K., Embrey, M. W., McCauley, J. A., Li, W., Lin, S., Liu, H., Dai, X., Baptista, M., Agnihotri, G., Columbus, J., Mei, H., Poirier, M., Zhou, X., Lin, Y., Yin, Z., Sanders, J. M., Drolet, R. E., Kern, J. T., Kennedy, M. E., Parker, E. M., Stamford, A. W., Nargund, R., Miller, M. W.	+	Authors: Scott, J.D., DeMong, D.E., Fell, M.J., Mirescu, C., Basu, K., Greshock, T.J., Morrow, J.A., Xiao, L., Hruza, A., Harris, J., Tiscia, H.E., Chang, R.K., Embrey, M.W., McCauley, J.A., Li, W., Lin, S., Liu, H., Dai, X., Baptista, M., Agnihotri, G., Columbus, J., Mei, H., Poirier, M., Zhou, X., Lin, Y., Yin, Z., Sanders, J.M., Drolet, R.E., Kern, J.T., Kennedy, M.E., Parker, E.M., Stamford, A.W., Nargund, R., Miller, M.W.

	Description: Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity		Description: Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity
Line 9:		Line 9:
	[[Category: Zhou, X]]		[[Category: Zhou, X]]
	[[Category: Nargund, R]]		[[Category: Nargund, R]]
-	[[Category: ~~Parker~~, E. M]]	+	[[Category: Demong, D.E]]
	[[Category: Baptista, M]]		[[Category: Baptista, M]]
-	[[Category: ~~Scott~~, ~~J. D]]~~	+	[[Category: Embrey, M.W]]
-	~~[[Category: Stamford, A~~. W]]	+	[[Category: Kennedy, M.E]]
-	[[Category: ~~Mccauley, J. A]]~~	+
-	~~[[Category: Chang~~, R. K]]	+
	[[Category: Poirier, M]]		[[Category: Poirier, M]]
		+	[[Category: Parker, E.M]]
		+	[[Category: Chang, R.K]]
	[[Category: Xiao, L]]		[[Category: Xiao, L]]
	[[Category: Basu, K]]		[[Category: Basu, K]]
	[[Category: Harris, J]]		[[Category: Harris, J]]
-	[[Category: ~~Kern~~, J. T]]	+	[[Category: Fell, M.J]]
	[[Category: Lin, S]]		[[Category: Lin, S]]
		+	[[Category: Miller, M.W]]
	[[Category: Liu, H]]		[[Category: Liu, H]]
-	[[Category: ~~Miller~~, M~~. W]]~~	+	[[Category: Sanders, J.M]]
-	~~[[Category: Tiscia, H. E~~]]	+
	[[Category: Columbus, J]]		[[Category: Columbus, J]]
		+	[[Category: Morrow, J.A]]
	[[Category: Hruza, A]]		[[Category: Hruza, A]]
-	[[Category: ~~Kennedy~~, M. E]]	+	[[Category: Stamford, A.W]]
-	[[Category: ~~Greshock~~, T. J]]	+	[[Category: Mccauley, J.A]]
		+	[[Category: Kern, J.T]]
	[[Category: Yin, Z]]		[[Category: Yin, Z]]
		+	[[Category: Tiscia, H.E]]
		+	[[Category: Greshock, T.J]]
	[[Category: Mirescu, C]]		[[Category: Mirescu, C]]
	[[Category: Lin, Y]]		[[Category: Lin, Y]]
	[[Category: Li, W]]		[[Category: Li, W]]
-	[[Category: ~~Demong D. E]]~~	+	[[Category: Scott, J.D]]
-	~~[[Category: Fell~~, M. J]]	+
-	~~[[Category: Drolet, R~~. E]]	+
	[[Category: Dai, X]]		[[Category: Dai, X]]
		+	[[Category: Drolet, R.E]]
	[[Category: Agnihotri, G]]		[[Category: Agnihotri, G]]
-	[[Category: Sanders, J. M]]
	[[Category: Mei, H]]		[[Category: Mei, H]]
-	[[Category: Embrey, M. W]]
-	[[Category: Morrow, J. A]]

OCA: Protected "5u6i" [edit=sysop:move=sysop]

2016-12-15T17:45:04Z

Protected "5u6i" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:45, 15 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u6i is ON HOLD Authors: Scott, J. D., DeMong D. E., Fell, M. J., Mirescu, C., Basu, K., Greshock, T. J., Morrow, J. A., Xiao, L., Hruza, A., Harris...

2016-12-15T17:45:02Z

New page: '''Unreleased structure''' The entry 5u6i is ON HOLD Authors: Scott, J. D., DeMong D. E., Fell, M. J., Mirescu, C., Basu, K., Greshock, T. J., Morrow, J. A., Xiao, L., Hruza, A., Harris...

New page

'''Unreleased structure'''

The entry 5u6i is ON HOLD

Authors: Scott, J. D., DeMong D. E., Fell, M. J., Mirescu, C., Basu, K., Greshock, T. J., Morrow, J. A., Xiao, L., Hruza, A., Harris, J., Tiscia, H. E., Chang, R. K., Embrey, M. W., McCauley, J. A., Li, W., Lin, S., Liu, H., Dai, X., Baptista, M., Agnihotri, G., Columbus, J., Mei, H., Poirier, M., Zhou, X., Lin, Y., Yin, Z., Sanders, J. M., Drolet, R. E., Kern, J. T., Kennedy, M. E., Parker, E. M., Stamford, A. W., Nargund, R., Miller, M. W.

Description: Discovery of MLi-2, an Orally Available and Selective LRRK2 Inhibitor that Reduces Brain Kinase Activity
[[Category: Unreleased Structures]]
[[Category: Zhou, X]]
[[Category: Nargund, R]]
[[Category: Parker, E. M]]
[[Category: Baptista, M]]
[[Category: Scott, J. D]]
[[Category: Stamford, A. W]]
[[Category: Mccauley, J. A]]
[[Category: Chang, R. K]]
[[Category: Poirier, M]]
[[Category: Xiao, L]]
[[Category: Basu, K]]
[[Category: Harris, J]]
[[Category: Kern, J. T]]
[[Category: Lin, S]]
[[Category: Liu, H]]
[[Category: Miller, M. W]]
[[Category: Tiscia, H. E]]
[[Category: Columbus, J]]
[[Category: Hruza, A]]
[[Category: Kennedy, M. E]]
[[Category: Greshock, T. J]]
[[Category: Yin, Z]]
[[Category: Mirescu, C]]
[[Category: Lin, Y]]
[[Category: Li, W]]
[[Category: Demong D. E]]
[[Category: Fell, M. J]]
[[Category: Drolet, R. E]]
[[Category: Dai, X]]
[[Category: Agnihotri, G]]
[[Category: Sanders, J. M]]
[[Category: Mei, H]]
[[Category: Embrey, M. W]]
[[Category: Morrow, J. A]]