4hbp: Difference between revisions
New page: '''Unreleased structure''' The entry 4hbp is ON HOLD Authors: Behnke, C., Skene, R.J. Description: Crystal Structure of FAAH in complex with inhibitor |
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==Crystal Structure of FAAH in complex with inhibitor== | |||
<StructureSection load='4hbp' size='340' side='right'caption='[[4hbp]], [[Resolution|resolution]] 2.91Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4hbp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HBP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HBP 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]] 2.91Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=17J:4-(3-PHENYL-1,2,4-THIADIAZOL-5-YL)-N-(PYRIDIN-3-YL)PIPERAZINE-1-CARBOXAMIDE'>17J</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=4hbp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hbp OCA], [https://pdbe.org/4hbp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hbp RCSB], [https://www.ebi.ac.uk/pdbsum/4hbp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hbp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FAAH1_RAT FAAH1_RAT] Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of piperazine ureas was designed, synthesized, and evaluated for their potential as novel orally available fatty acid amide hydrolase (FAAH) inhibitors that are therapeutically effective against pain. We carried out an optimization study of the lead compound 3 to improve its DMPK profile as well as in vitro potency. We identified the thiazole compound 60j with potent inhibitory activity, high brain permeability, and good bioavailability. Compound 60j showed a potent and dose-dependent anti-nociceptive effect in the acetic acid-induced writhing test in mice. | |||
Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors.,Kono M, Matsumoto T, Kawamura T, Nishimura A, Kiyota Y, Oki H, Miyazaki J, Igaki S, Behnke CA, Shimojo M, Kori M Bioorg Med Chem. 2013 Jan 1;21(1):28-41. doi: 10.1016/j.bmc.2012.11.006. Epub, 2012 Nov 15. PMID:23218778<ref>PMID:23218778</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4hbp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Fatty acid amide hydrolase|Fatty acid amide hydrolase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Behnke C]] | |||
[[Category: Skene RJ]] | |||
Latest revision as of 18:03, 20 September 2023
Crystal Structure of FAAH in complex with inhibitorCrystal Structure of FAAH in complex with inhibitor
Structural highlights
FunctionFAAH1_RAT Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates (By similarity). Publication Abstract from PubMedA series of piperazine ureas was designed, synthesized, and evaluated for their potential as novel orally available fatty acid amide hydrolase (FAAH) inhibitors that are therapeutically effective against pain. We carried out an optimization study of the lead compound 3 to improve its DMPK profile as well as in vitro potency. We identified the thiazole compound 60j with potent inhibitory activity, high brain permeability, and good bioavailability. Compound 60j showed a potent and dose-dependent anti-nociceptive effect in the acetic acid-induced writhing test in mice. Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors.,Kono M, Matsumoto T, Kawamura T, Nishimura A, Kiyota Y, Oki H, Miyazaki J, Igaki S, Behnke CA, Shimojo M, Kori M Bioorg Med Chem. 2013 Jan 1;21(1):28-41. doi: 10.1016/j.bmc.2012.11.006. Epub, 2012 Nov 15. PMID:23218778[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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