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New page: '''Unreleased structure''' The entry 4pm0 is ON HOLD Authors: Kawai, K., Endo, Y., Asano, Y., Amano, S., Sawada, K., Ueo, N., Takahashi, N., Sonoda, Y., Kamei, N., Nagata, N. Descripti... |
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The | ==PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative== | ||
<StructureSection load='4pm0' size='340' side='right'caption='[[4pm0]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pm0]] is a 1 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=4PM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PM0 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32V:2-(CYCLOPENTYLAMINO)-3-ETHYL-7-ETHYNYLTHIENO[3,2-D]PYRIMIDIN-4(3H)-ONE'>32V</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=4pm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pm0 OCA], [https://pdbe.org/4pm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pm0 RCSB], [https://www.ebi.ac.uk/pdbsum/4pm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pm0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PDE7A_HUMAN PDE7A_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.<ref>PMID:19350606</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy. | |||
Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors.,Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N J Med Chem. 2014 Nov 19. PMID:25383422<ref>PMID:25383422</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4pm0" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Amano S]] | |||
[[Category: Asano T]] | |||
[[Category: Endo Y]] | |||
[[Category: Kamei N]] | |||
[[Category: Kawai K]] | |||
[[Category: Nagata N]] | |||
[[Category: Sawada K]] | |||
[[Category: Sonoda Y]] | |||
[[Category: Takahashi N]] | |||
[[Category: Ueo N]] | |||
Latest revision as of 18:00, 8 November 2023
PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivativePDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative
Structural highlights
FunctionPDE7A_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.[1] Publication Abstract from PubMedThe discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy. Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors.,Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N J Med Chem. 2014 Nov 19. PMID:25383422[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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