7zqx
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Human galectin-3c in complex with a galactose derivative== | |
| + | <StructureSection load='7zqx' size='340' side='right'caption='[[7zqx]], [[Resolution|resolution]] 1.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7zqx]] is a 1 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=7ZQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZQX FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JU0:(2~{R},3~{R},4~{S},5~{R},6~{R})-2-(5-bromanylpyridin-3-yl)sulfanyl-6-(hydroxymethyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol'>JU0</scene>, <scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=7zqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zqx OCA], [https://pdbe.org/7zqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zqx RCSB], [https://www.ebi.ac.uk/pdbsum/7zqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zqx ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LEG3_HUMAN LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.<ref>PMID:15181153</ref> <ref>PMID:19594635</ref> <ref>PMID:19616076</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found a high affinity (nM) thiodigalactoside GB0139 which currently is in clinical development (PhIIb) as an inhaled treatment of idiopathic pulmonary fibrosis. To enable treatment of systemically galectin-3 driven disease, we here present the first series of selective galectin-3 inhibitors combining high affinity (nM) with oral bioavailability. This was achieved by optimizing galectin-3 specificity and physical chemical parameters for a series of disubstituted monogalactosides. Further characterization showed that this class of compounds reduced profibrotic gene expression in liver myofibroblasts and displayed antifibrotic activity in CCl4-induced liver fibrosis and bleomycin-induced lung fibrosis mouse models. On the basis of the overall pharmacokinetic, pharmacodynamic, and safety profile, GB1211 was selected as the clinical candidate and is currently in phase IIa clinical trials as a potential therapy for liver cirrhosis and cancer. | ||
| - | + | Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease.,Zetterberg FR, MacKinnon A, Brimert T, Gravelle L, Johnsson RE, Kahl-Knutson B, Leffler H, Nilsson UJ, Pedersen A, Peterson K, Roper JA, Schambye H, Slack RJ, Tantawi S J Med Chem. 2022 Oct 13;65(19):12626-12638. doi: 10.1021/acs.jmedchem.2c00660., Epub 2022 Sep 26. PMID:36154172<ref>PMID:36154172</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7zqx" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hakansson M]] | ||
| + | [[Category: Logan DT]] | ||
| + | [[Category: Nilsson UJ]] | ||
| + | [[Category: Zetterberg F]] | ||
Revision as of 07:22, 3 November 2022
Human galectin-3c in complex with a galactose derivative
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