6x8f: Difference between revisions

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-'''Unreleased structure'''
-The entry 6x8f is ON HOLD
+==Crystal structure of TYK2 with Compound 11==
+<StructureSection load='6x8f' size='340' side='right'caption='[[6x8f]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X8F 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]] 2.15&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=UWP:[3-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]-1H-pyrazol-1-yl}-1-(2,2,2-trifluoroethyl)azetidin-3-yl]acetonitrile'>UWP</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=6x8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x8f OCA], [https://pdbe.org/6x8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x8f RCSB], [https://www.ebi.ac.uk/pdbsum/6x8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x8f ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family that regulates signal transduction downstream of receptors for the IL-23/IL-12 pathways and type I interferon family, where it pairs with JAK2 or JAK1, respectively. On the basis of human genetic and emerging clinical data, a selective TYK2 inhibitor provides an opportunity to treat autoimmune diseases delivering a potentially differentiated clinical profile compared to currently approved JAK inhibitors. The discovery of an ATP-competitive pyrazolopyrazinyl series of TYK2 inhibitors was accomplished through computational and structurally enabled design starting from a known kinase hinge binding motif. With understanding of PK/PD relationships, a target profile balancing TYK2 potency and selectivity over off-target JAK2 was established. Lead optimization involved modulating potency, selectivity, and ADME properties which led to the identification of the clinical candidate PF-06826647 (22).
-Authors: Vajdos, F.F., Knafels, J.D.
+Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases.,Gerstenberger BS, Ambler C, Arnold EP, Banker ME, Brown MF, Clark JD, Dermenci A, Dowty ME, Fensome A, Fish S, Hayward MM, Hegen M, Hollingshead BD, Knafels JD, Lin DW, Lin TH, Owen DR, Saiah E, Sharma R, Vajdos FF, Xing L, Yang X, Yang X, Wright SW J Med Chem. 2020 Aug 25. doi: 10.1021/acs.jmedchem.0c00948. PMID:32787094<ref>PMID:32787094</ref>
-Description: Crystal structure of TYK2 with Compound 11
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Vajdos, F.F]]
+<div class="pdbe-citations 6x8f" style="background-color:#fffaf0;"></div>
-[[Category: Knafels, J.D]]
+==See Also==
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Knafels JD]]
+[[Category: Vajdos FF]]