4tpp: Difference between revisions
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==2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors== | |||
<StructureSection load='4tpp' size='340' side='right'caption='[[4tpp]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4tpp]] 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=4TPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TPP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=35D:1-[4-(3-{[1-(QUINOLIN-2-YL)AZETIDIN-3-YL]OXY}QUINOXALIN-2-YL)PIPERIDIN-1-YL]ETHANONE'>35D</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4tpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpp OCA], [https://pdbe.org/4tpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tpp RCSB], [https://www.ebi.ac.uk/pdbsum/4tpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tpp ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum. | |||
Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility.,Rzasa RM, Frohn MJ, Andrews KL, Chmait S, Chen N, Clarine JG, Davis C, Eastwood HA, Horne DB, Hu E, Jones AD, Kaller MR, Kunz RK, Miller S, Monenschein H, Nguyen T, Pickrell AJ, Porter A, Reichelt A, Zhao X, Treanor JJ, Allen JR Bioorg Med Chem. 2014 Oct 22;22(23):6570-6585. doi: 10.1016/j.bmc.2014.10.013. PMID:25456383<ref>PMID:25456383</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4tpp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chmait S]] | |||
Latest revision as of 00:47, 28 December 2023
2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors
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