4xy2 - Revision history

OCA at 09:02, 20 March 2024

OCA — Wed, 20 Mar 2024 09:02:59 GMT

←Older revision		Revision as of 09:02, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.03Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [https://pdbe.org/4xy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [https://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [https://pdbe.org/4xy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [https://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>		[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	We synthesized several biaryl derivatives as PDE10A inhibitors to prevent phototoxicity of 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (1) and found that the energy difference between the energy-minimized conformation and the coplanar conformation of the biaryl moiety helped facilitate prediction of the phototoxic potential of biaryl compounds. Replacement of the quinoline ring of 1 with N-methyl benzimidazole increased this energy difference and prevented phototoxicity in the 3T3 NRU test. Further optimization identified 1-methyl-5-(1-methyl-3-{[4-(1-methyl-1H-benzimidazol-4-yl)phenoxy]methyl}-1H-pyra zol-4-yl)pyridin-2(1H)-one (38b). Compound 38b exhibited good selectivity against other PDEs, and oral administration of 38b improved visual-recognition memory deficit in mice at doses of 0.001 and 0.003mg/kg in the novel object recognition test. ASP9436 (sesquiphosphate of 38b) may therefore be used for the treatment of schizophrenia with a low risk of phototoxicity.
-
-	Addressing phototoxicity observed in a novel series of biaryl derivatives: Discovery of potent, selective and orally active phosphodiesterase 10A inhibitor ASP9436.,Hamaguchi W, Masuda N, Miyamoto S, Kikuchi S, Narazaki F, Shiina Y, Seo R, Amano Y, Mihara T, Moriguchi H, Hattori K Bioorg Med Chem. 2015 Jul 1;23(13):3351-67. doi: 10.1016/j.bmc.2015.04.052. Epub , 2015 Apr 25. PMID:25960322<ref>PMID:25960322</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4xy2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 17:58, 26 April 2023

OCA — Wed, 26 Apr 2023 17:58:01 GMT

←Older revision		Revision as of 17:58, 26 April 2023
Line 3:		Line 3:
	<StructureSection load='4xy2' size='340' side='right'caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>		<StructureSection load='4xy2' size='340' side='right'caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [https://pdbe.org/4xy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [https://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [~~http~~://pdbe.org/4xy2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>	+	[https://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Amano, Y]]	+	[[Category: Amano Y]]
-	[[Category: Honbou, K]]	+	[[Category: Honbou K]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Phosphodiesterase~~]]	+

OCA at 08:40, 5 February 2020

OCA — Wed, 05 Feb 2020 08:40:51 GMT

←Older revision		Revision as of 08:40, 5 February 2020
Line 21:		Line 21:

	==See Also==		==See Also==
-	*[[Phosphodiesterase\|Phosphodiesterase]]	+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
-	*[[Phosphofructokinase ~~(PFK)~~\|Phosphofructokinase ~~(PFK)~~]]	+	*[[Phosphofructokinase 3D structures\|Phosphofructokinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 23:59, 5 June 2019

OCA — Wed, 05 Jun 2019 23:59:14 GMT

←Older revision		Revision as of 23:59, 5 June 2019
Line 1:		Line 1:

	==Crystal structure of PDE10A in complex with ASP9436==		==Crystal structure of PDE10A in complex with ASP9436==
-	<StructureSection load='4xy2' size='340' side='right' caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>	+	<StructureSection load='4xy2' size='340' side='right'caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDE10A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [http://pdbe.org/4xy2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [http://pdbe.org/4xy2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</span></td></tr>
	</table>		</table>
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4xy2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4xy2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase\|Phosphodiesterase]]
		+	*[[Phosphofructokinase (PFK)\|Phosphofructokinase (PFK)]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Amano, Y]]		[[Category: Amano, Y]]
	[[Category: Honbou, K]]		[[Category: Honbou, K]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Phosphodiesterase]]		[[Category: Phosphodiesterase]]

OCA at 14:23, 29 March 2017

OCA — Wed, 29 Mar 2017 14:23:19 GMT

←Older revision		Revision as of 14:23, 29 March 2017
Line 1:		Line 1:
		+
	==Crystal structure of PDE10A in complex with ASP9436==		==Crystal structure of PDE10A in complex with ASP9436==
	<StructureSection load='4xy2' size='340' side='right' caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>		<StructureSection load='4xy2' size='340' side='right' caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4xy2 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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [http://pdbe.org/4xy2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4xy2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xy2 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 17:
	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 4xy2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:59, 17 June 2015

OCA — Wed, 17 Jun 2015 14:59:28 GMT

←Older revision		Revision as of 14:59, 17 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of PDE10A in complex with ASP9436==
		+	<StructureSection load='4xy2' size='340' side='right' caption='[[4xy2]], [[Resolution\|resolution]] 2.03Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4xy2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XY2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XY2 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=490:1-METHYL-5-(1-METHYL-3-{[4-(1-METHYL-1H-BENZIMIDAZOL-4-YL)PHENOXY]METHYL}-1H-PYRAZOL-4-YL)PYRIDIN-2(1H)-ONE'>490</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4xy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xy2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xy2 RCSB], [http://www.ebi.ac.uk/pdbsum/4xy2 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDE10_HUMAN PDE10_HUMAN]] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.<ref>PMID:17389385</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We synthesized several biaryl derivatives as PDE10A inhibitors to prevent phototoxicity of 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (1) and found that the energy difference between the energy-minimized conformation and the coplanar conformation of the biaryl moiety helped facilitate prediction of the phototoxic potential of biaryl compounds. Replacement of the quinoline ring of 1 with N-methyl benzimidazole increased this energy difference and prevented phototoxicity in the 3T3 NRU test. Further optimization identified 1-methyl-5-(1-methyl-3-{[4-(1-methyl-1H-benzimidazol-4-yl)phenoxy]methyl}-1H-pyra zol-4-yl)pyridin-2(1H)-one (38b). Compound 38b exhibited good selectivity against other PDEs, and oral administration of 38b improved visual-recognition memory deficit in mice at doses of 0.001 and 0.003mg/kg in the novel object recognition test. ASP9436 (sesquiphosphate of 38b) may therefore be used for the treatment of schizophrenia with a low risk of phototoxicity.

-	~~The entry 4xy2 is ON HOLD until Paper Publication~~	+	Addressing phototoxicity observed in a novel series of biaryl derivatives: Discovery of potent, selective and orally active phosphodiesterase 10A inhibitor ASP9436.,Hamaguchi W, Masuda N, Miyamoto S, Kikuchi S, Narazaki F, Shiina Y, Seo R, Amano Y, Mihara T, Moriguchi H, Hattori K Bioorg Med Chem. 2015 Jul 1;23(13):3351-67. doi: 10.1016/j.bmc.2015.04.052. Epub , 2015 Apr 25. PMID:25960322<ref>PMID:25960322</ref>

-	~~Authors: Amano~~, Y.~~, Honbou, K~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure of PDE10A in complex with ASP9436~~	+	== References ==
-	~~[[Category: Unreleased Structures]]~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Amano, Y]]		[[Category: Amano, Y]]
	[[Category: Honbou, K]]		[[Category: Honbou, K]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Phosphodiesterase]]

OCA at 10:07, 11 March 2015

OCA — Wed, 11 Mar 2015 10:07:08 GMT

←Older revision		Revision as of 10:07, 11 March 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4xy2 is ON HOLD	+	The entry 4xy2 is ON HOLD until Paper Publication

	Authors: Amano, Y., Honbou, K.		Authors: Amano, Y., Honbou, K.

OCA: Protected "4xy2" [edit=sysop:move=sysop]

OCA — Thu, 12 Feb 2015 10:50:44 GMT

Protected "4xy2" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:50, 12 February 2015

OCA: New page: '''Unreleased structure''' The entry 4xy2 is ON HOLD Authors: Amano, Y., Honbou, K. Description: Crystal structure of PDE10A in complex with ASP9436 Category: Unreleased Structures...

OCA — Thu, 12 Feb 2015 10:50:43 GMT

New page: '''Unreleased structure''' The entry 4xy2 is ON HOLD Authors: Amano, Y., Honbou, K. Description: Crystal structure of PDE10A in complex with ASP9436 Category: Unreleased Structures...

New page

'''Unreleased structure'''

The entry 4xy2 is ON HOLD

Authors: Amano, Y., Honbou, K.

Description: Crystal structure of PDE10A in complex with ASP9436
[[Category: Unreleased Structures]]
[[Category: Amano, Y]]
[[Category: Honbou, K]]