9h4d
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of IL-17A in complex with compound 18== | |
| + | <StructureSection load='9h4d' size='340' side='right'caption='[[9h4d]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9h4d]] is a 2 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=9H4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9H4D 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]] 2.117Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ISH:(~{E})-~{N}-[(1~{S})-1-[4,4-bis(fluoranyl)cyclohexyl]-2-oxidanylidene-2-[[5-[(2-oxidanylidene-3~{H}-benzimidazol-1-yl)methyl]-1,3-thiazol-2-yl]amino]ethyl]-3-cyclopropyl-2-fluoranyl-prop-2-enamide'>A1ISH</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=9h4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9h4d OCA], [https://pdbe.org/9h4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9h4d RCSB], [https://www.ebi.ac.uk/pdbsum/9h4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9h4d ProSAT]</span></td></tr> | ||
| + | </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 == | ||
| + | The pro-inflammatory cytokine interleukin-17A (IL-17) plays an important role in the body's defense against bacterial and fungal infections. However, overexpression of IL-17 has been associated with several diseases, including rheumatoid arthritis, asthma, psoriasis, and even cancer. The role of IL-17 in psoriasis has been confirmed by clinical use of IL-17 antibodies, e. g. secukinumab (Cosentyx((R))). Ongoing research is focused on discovering low molecular weight IL-17 inhibitors. In this publication, we present thiazole-based IL-17 inhibitors discovered through a scaffold-morphing strategy. This strategy involved ring-opening of a known scaffold and utilization of a chalcogen interaction between thiazole-sulfur and central amide-oxygen to maintain the coplanar conformation found in the parent compound. The new scaffold enabled the generation of highly potent compounds with good overall profile. The optimized compounds 11 and 15 demonstrated good exposure in rats after oral dosing. Importantly, compound 11 exhibited no adverse effects in a rat tolerability study after a four-day administration of up to 300 mg/kg/day. | ||
| - | + | Thiazole-Based IL-17 Inhibitors Discovered by Scaffold Morphing.,Velcicky J, Ngo E, Bauer MR, Meyer A, Schlapbach A, Racine S, Orain D, Pflieger D, Teixeira-Fouchard S, Dubois C, Goetz A, Steiner R, Palmieri M, Bussenault A, Stringer R, Larger P, Riek S, Schmutz P, Lehmann S, Scheufler C, Rondeau JM, Burkhart C, Knoepfel T, Gommermann N ChemMedChem. 2024 Dec 23:e202400851. doi: 10.1002/cmdc.202400851. PMID:39715021<ref>PMID:39715021</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9h4d" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lehmann S]] | ||
| + | [[Category: Rondeau JM]] | ||
| + | [[Category: Scheufler C]] | ||
Current revision
Crystal structure of IL-17A in complex with compound 18
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