6zis: Difference between revisions
New page: '''Unreleased structure''' The entry 6zis is ON HOLD Authors: Southall, S.M. Description: Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor... |
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The | ==Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor== | ||
<StructureSection load='6zis' size='340' side='right'caption='[[6zis]], [[Resolution|resolution]] 1.73Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZIS 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]] 1.73Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3N6:N-{(1S)-5-AMINO-1-[(4-PYRIDIN-4-YLPIPERAZIN-1-YL)CARBONYL]PENTYL}-3,5-DIBROMO-NALPHA-{[4-(2-OXO-1,4-DIHYDROQUINAZOLIN-3(2H)-YL)PIPERIDIN-1-YL]CARBONYL}-D-TYROSINAMIDE'>3N6</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=6zis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zis OCA], [https://pdbe.org/6zis PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zis RCSB], [https://www.ebi.ac.uk/pdbsum/6zis PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zis ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Structure-based drug design enabled the discovery of 8, HTL22562, a calcitonin gene-related peptide (CGRP) receptor antagonist. The structure of 8 complexed with the CGRP receptor was determined at a 1.6 A resolution. Compound 8 is a highly potent, selective, metabolically stable, and soluble compound suitable for a range of administration routes that have the potential to provide rapid systemic exposures with resultant high levels of receptor coverage (e.g., subcutaneous). The low lipophilicity coupled with a low anticipated clinically efficacious plasma exposure for migraine also suggests a reduced potential for hepatotoxicity. These properties have led to 8 being selected as a clinical candidate for acute treatment of migraine. | |||
Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-( pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrosp iro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine.,Bucknell SJ, Ator MA, Brown AJH, Brown J, Cansfield AD, Cansfield JE, Christopher JA, Congreve M, Cseke G, Deflorian F, Jones CR, Mason JS, O'Brien MA, Ott GR, Pickworth M, Southall SM J Med Chem. 2020 Jul 8. doi: 10.1021/acs.jmedchem.0c01003. PMID:32558564<ref>PMID:32558564</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Southall | <div class="pdbe-citations 6zis" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Southall SM]] | |||
Latest revision as of 13:47, 23 October 2024
Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitorCrystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor
Structural highlights
Publication Abstract from PubMedStructure-based drug design enabled the discovery of 8, HTL22562, a calcitonin gene-related peptide (CGRP) receptor antagonist. The structure of 8 complexed with the CGRP receptor was determined at a 1.6 A resolution. Compound 8 is a highly potent, selective, metabolically stable, and soluble compound suitable for a range of administration routes that have the potential to provide rapid systemic exposures with resultant high levels of receptor coverage (e.g., subcutaneous). The low lipophilicity coupled with a low anticipated clinically efficacious plasma exposure for migraine also suggests a reduced potential for hepatotoxicity. These properties have led to 8 being selected as a clinical candidate for acute treatment of migraine. Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-( pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrosp iro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine.,Bucknell SJ, Ator MA, Brown AJH, Brown J, Cansfield AD, Cansfield JE, Christopher JA, Congreve M, Cseke G, Deflorian F, Jones CR, Mason JS, O'Brien MA, Ott GR, Pickworth M, Southall SM J Med Chem. 2020 Jul 8. doi: 10.1021/acs.jmedchem.0c01003. PMID:32558564[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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