7amg: Difference between revisions

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<StructureSection load='7amg' size='340' side='right'caption='[[7amg]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
<StructureSection load='7amg' size='340' side='right'caption='[[7amg]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7amg]] is a 4 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=7AMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AMG FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AMG 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]] 3.18&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RMQ:(3~{R})-4-[4-[[(2~{S})-2-[[2,2-bis(fluoranyl)-2-phenyl-ethanoyl]amino]-3-(2-chlorophenyl)propanoyl]amino]phenyl]-3-[[(2~{S})-3-methyl-2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethanoylamino]butanoyl]amino]butanoic+acid'>RMQ</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RMQ:(3~{R})-4-[4-[[(2~{S})-2-[[2,2-bis(fluoranyl)-2-phenyl-ethanoyl]amino]-3-(2-chlorophenyl)propanoyl]amino]phenyl]-3-[[(2~{S})-3-methyl-2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethanoylamino]butanoyl]amino]butanoic+acid'>RMQ</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=7amg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amg OCA], [https://pdbe.org/7amg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7amg RCSB], [https://www.ebi.ac.uk/pdbsum/7amg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7amg ProSAT]</span></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=7amg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amg OCA], [https://pdbe.org/7amg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7amg RCSB], [https://www.ebi.ac.uk/pdbsum/7amg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7amg ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interleukin 17A (IL-17A) is an interleukin cytokine whose dysregulation is implicated in autoimmune disorders such as psoriasis, and monoclonal antibodies against the IL-17A pathway are now well-established and very effective treatments. This article outlines the work that led to the identification of 23 as an oral, small-molecule protein-protein interaction modulator (PPIm) clinical development candidate. Protein crystallography provided knowledge of the key binding interactions between small-molecule ligands and the IL-17A dimer, and this helped in the multiparameter optimization toward identifying an orally bioavailable, Rule of 5 compliant PPIm of IL-17A. Overlap of early ligands led to a series of benzhydrylglycine-containing compounds that allowed the identification of dimethylpyrazole as a key substituent that gave PPIm with oral bioavailability. Exploration of the amino acid portion of the structure then led to dicyclopropylalanine as a group that gave potent and metabolically stable compounds, including the development candidate 23.
Discovery of an Oral, Rule of 5 Compliant, Interleukin 17A Protein-Protein Interaction Modulator for the Potential Treatment of Psoriasis and Other Inflammatory Diseases.,Andrews MD, Dack KN, de Groot MJ, Lambert M, Sennbro CJ, Larsen M, Stahlhut M J Med Chem. 2022 Jul 14;65(13):8828-8842. doi: 10.1021/acs.jmedchem.2c00422. Epub, 2022 Jun 29. PMID:35767390<ref>PMID:35767390</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7amg" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Andrews MD]]
[[Category: Andrews MD]]

Latest revision as of 08:34, 17 October 2024

IL-17A in complex with small molecule modulators

7amg, resolution 3.18Å

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