9v82: Difference between revisions
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New page: '''Unreleased structure''' The entry 9v82 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Local refine map of HEP-50768-bound MRGPRX4== | |||
<StructureSection load='9v82' size='340' side='right'caption='[[9v82]], [[Resolution|resolution]] 2.56Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9v82]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9V82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9V82 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.56Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L9Y:5-[2-fluoranyl-3-[(2~{S})-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]phenyl]-1~{H}-1,2,3,4-tetrazole'>A1L9Y</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=9v82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9v82 OCA], [https://pdbe.org/9v82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9v82 RCSB], [https://www.ebi.ac.uk/pdbsum/9v82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9v82 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/MRGX4_HUMAN MRGX4_HUMAN] Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain. Potently activated by enkephalins (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Chronic itch, particularly in cholestatic and uremic conditions, poses a notable clinical burden, yet treatment options remain inadequate. MRGPRX4 (hX4), a bile-acid-sensing G-protein-coupled receptor predominantly expressed in human sensory neurons, has emerged as a critical mediator of cholestatic pruritus. Here we identified and characterized HEP-50768, a potent and selective small-molecule inverse agonist of hX4 through high-throughput screening and structure-activity optimization. Structural elucidation through cryo-electron microscopy of the hX4-inverse agonist complex structure revealed the unique binding mode and inhibitory mechanism of HEP-50768. In hX4-humanized rats, HEP-50768 robustly suppressed bile-acid-induced pruritic behaviors. Comprehensive preclinical absorption, distribution, metabolism, excretion and safety profiling was performed in both rats and monkeys, and these findings establish HEP-50768 as a promising therapeutic candidate for chronic itch, supporting its advancement to clinical evaluation. | |||
Development of a clinically viable MRGPRX4 inverse agonist for cholestatic itch treatment.,Yang J, Shen R, Wang C, Zhu W, Ke H, Fan J, Zhang M, Liu Y, Li S, Li G, Wang X, Li Y, Cao C, Lei X Nat Chem Biol. 2026 Apr 9. doi: 10.1038/s41589-026-02195-0. PMID:41957282<ref>PMID:41957282</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9v82" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Cao C]] | |||
[[Category: Wang C]] | |||
[[Category: Zhang M]] | |||
Latest revision as of 07:41, 7 October 2026
Local refine map of HEP-50768-bound MRGPRX4
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