6a3n: Difference between revisions
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==Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2== | |||
<StructureSection load='6a3n' size='340' side='right'caption='[[6a3n]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6a3n]] 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=6A3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A3N 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]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9Q9:1-cyclopentyl-6-({(2R)-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxopropan-2-yl}amino)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one'>9Q9</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=6a3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a3n OCA], [https://pdbe.org/6a3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a3n RCSB], [https://www.ebi.ac.uk/pdbsum/6a3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a3n ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PDE9A_HUMAN PDE9A_HUMAN] Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.<ref>PMID:18757755</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition. | |||
Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.,Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555<ref>PMID:30916555</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6a3n" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen YP]] | |||
[[Category: Luo HB]] | |||
[[Category: Wu YN]] | |||
[[Category: Zhou Q]] | |||
Latest revision as of 12:17, 22 November 2023
Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2
Structural highlights
FunctionPDE9A_HUMAN Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.[1] Publication Abstract from PubMedTo identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition. Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.,Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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