View source for 8oeg


==PDE4B bound to MAPI compound 92a==
<StructureSection load='8oeg' size='340' side='right'caption='[[8oeg]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oeg]] 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=8OEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OEG 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]] 1.89&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VL9:[(1~{S})-2-[3,5-bis(chloranyl)-1-oxidanyl-pyridin-4-yl]-1-(3,4-dimethoxyphenyl)ethyl]+5-[[[(1~{R})-2-[[(3~{R})-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxidanylidene-1-phenyl-ethyl]amino]methyl]thiophene-2-carboxylate'>VL9</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=8oeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oeg OCA], [https://pdbe.org/8oeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oeg RCSB], [https://www.ebi.ac.uk/pdbsum/8oeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oeg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PDE4B_HUMAN PDE4B_HUMAN] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In this paper, we report the discovery of dual M(3) antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001 series with a muscarinic scaffold through a common linking ring could generate compounds active versus both the transmembrane M(3) receptor and the intracellular PDE4 enzyme. Two chemical series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M(3) nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo (inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro (inhibition of TNFalpha release). Among the best compounds, compound 92a achieved the goal of demonstrating in vivo efficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.

Discovery of M(3) Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease.,Armani E, Rizzi A, Capaldi C, De Fanti R, Delcanale M, Villetti G, Marchini G, Pisano AR, Pitozzi V, Pittelli MG, Trevisani M, Salvadori M, Cenacchi V, Puccini P, Amadei F, Pappani A, Civelli M, Patacchini R, Baker-Glenn CAG, Van de Poel H, Blackaby WP, Nash K, Amari G J Med Chem. 2021 Jul 8;64(13):9100-9119. doi: 10.1021/acs.jmedchem.1c00204. Epub , 2021 Jun 18. PMID:34142835<ref>PMID:34142835</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8oeg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Armani E]]
[[Category: Rizzi A]]