4zo5
From Proteopedia
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| - | ''' | + | ==PDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dione== |
| + | <StructureSection load='4zo5' size='340' side='right' caption='[[4zo5]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4zo5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZO5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZO5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4PX:3-(1-HYDROXY-2-METHYLPROPAN-2-YL)-5-PHENYL-3,5-DIHYDRO-1H-IMIDAZO[4,5-C][1,8]NAPHTHYRIDINE-2,4-DIONE'>4PX</scene>, <scene name='pdbligand=4Q0:2-{2-[3-(4-METHOXYPHENYL)-4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL]ETHYL}-4-(PROPAN-2-YLOXY)-1H-ISOINDOLE-1,3(2H)-DIONE'>4Q0</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=4zo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zo5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zo5 RCSB], [http://www.ebi.ac.uk/pdbsum/4zo5 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 == | ||
| + | Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [11C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey. | ||
| - | + | Discovery of [C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors.,Cox CD, Hostetler ED, Flores BA, Evelhoch JL, Fan H, Gantert L, Holahan M, Eng W, Joshi A, McGaughey G, Meng X, Purcell M, Raheem IT, Riffel K, Yan Y, Renger JJ, Smith SM, Coleman PJ Bioorg Med Chem Lett. 2015 Jun 1. pii: S0960-894X(15)00554-5. doi:, 10.1016/j.bmcl.2015.05.080. PMID:26077491<ref>PMID:26077491</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Yan, Y]] | [[Category: Yan, Y]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Phosphodiesterase inhibitor]] | ||
Revision as of 14:41, 12 August 2015
PDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dione
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