6msc: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 1: Line 1:


==Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors==
==Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors==
<StructureSection load='6msc' size='340' side='right' caption='[[6msc]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
<StructureSection load='6msc' size='340' side='right'caption='[[6msc]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6msc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MSC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MSC FirstGlance]. <br>
<table><tr><td colspan='2'>[[6msc]] 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=6MSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MSC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JY7:8-fluoro-6-methoxy-3-methyl-1-(3-methylpyridin-4-yl)-3H-pyrazolo[3,4-c]cinnoline'>JY7</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]] 2.36&#8491;</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=6msc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6msc OCA], [http://pdbe.org/6msc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6msc RCSB], [http://www.ebi.ac.uk/pdbsum/6msc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6msc ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JY7:8-fluoro-6-methoxy-3-methyl-1-(3-methylpyridin-4-yl)-3H-pyrazolo[3,4-c]cinnoline'>JY7</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=6msc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6msc OCA], [https://pdbe.org/6msc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6msc RCSB], [https://www.ebi.ac.uk/pdbsum/6msc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6msc 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;">
== Publication Abstract from PubMed ==
Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.


Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.,Geneste H, Drescher K, Jakob C, Laplanche L, Ochse M, Torrent M Bioorg Med Chem Lett. 2018 Dec 19. pii: S0960-894X(18)30976-4. doi:, 10.1016/j.bmcl.2018.12.029. PMID:30587449<ref>PMID:30587449</ref>
==See Also==
 
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6msc" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Jakob, C G]]
[[Category: Homo sapiens]]
[[Category: Hydrolase]]
[[Category: Large Structures]]
[[Category: Phosphodiesterase]]
[[Category: Jakob CG]]

Latest revision as of 17:44, 13 March 2024

Novel, potent, selective and brain penetrant phosphodiesterase 10A inhibitorsNovel, potent, selective and brain penetrant phosphodiesterase 10A inhibitors

Structural highlights

6msc is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.36Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

See Also

References

  1. ↑ Wang H, Liu Y, Hou J, Zheng M, Robinson H, Ke H. Structural insight into substrate specificity of phosphodiesterase 10. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5782-7. Epub 2007 Mar 26. PMID:17389385

6msc, resolution 2.36Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6msc&oldid=4092126"