4gfo
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gfo]] 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=4GFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GFO FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gfo]] 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=4GFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GFO FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0X2:2,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPYRIDIN-4-YL)BENZAMIDE'>0X2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0X2:2,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPYRIDIN-4-YL)BENZAMIDE'>0X2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4gfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gfo OCA], [https://pdbe.org/4gfo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gfo RCSB], [https://www.ebi.ac.uk/pdbsum/4gfo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gfo 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=4gfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gfo OCA], [https://pdbe.org/4gfo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gfo RCSB], [https://www.ebi.ac.uk/pdbsum/4gfo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gfo ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref> | [https://www.uniprot.org/uniprot/TYK2_HUMAN TYK2_HUMAN] Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.<ref>PMID:7526154</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors, revealed pyridine 1 as a promising starting point for lead identification. Initial expansion of 3 separate regions of the molecule led to eventual identification of cyclopropyl amide 46, a potent lead analog with good kinase selectivity, physicochemical properties, and pharmacokinetic profile. Analysis of the binding modes of the series in TYK2 and JAK2 crystal structures revealed key interactions leading to good TYK2 potency and design options for future optimization of selectivity. | ||
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| - | Lead identification of novel and selective TYK2 inhibitors.,Liang J, Tsui V, Van Abbema A, Bao L, Barrett K, Beresini M, Berezhkovskiy L, Blair WS, Chang C, Driscoll J, Eigenbrot C, Ghilardi N, Gibbons P, Halladay J, Johnson A, Kohli PB, Lai Y, Liimatta M, Mantik P, Menghrajani K, Murray J, Sambrone A, Xiao Y, Shia S, Shin Y, Smith J, Sohn S, Stanley M, Ultsch M, Zhang B, Wu LC, Magnuson S Eur J Med Chem. 2013 May 14;67C:175-187. doi: 10.1016/j.ejmech.2013.03.070. PMID:23867602<ref>PMID:23867602</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gfo" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
TYK2 kinase (JH1 domain) with 2,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPYRIDIN-4-YL)BENZAMIDE
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