8br6

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'''Unreleased structure'''
 
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The entry 8br6 is ON HOLD until Paper Publication
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==Discovery of IRAK4 Inhibitor 40==
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<StructureSection load='8br6' size='340' side='right'caption='[[8br6]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8br6]] 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=8BR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BR6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.167&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=R6I:~{N}-[6-methoxy-2-(2-methylsulfonylethyl)-1,3-dihydroindazol-5-yl]-6-(2-oxidanylpropan-2-yl)pyridine-2-carboxamide'>R6I</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8br6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8br6 OCA], [https://pdbe.org/8br6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8br6 RCSB], [https://www.ebi.ac.uk/pdbsum/8br6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8br6 ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate inflammatory processes. Here, we describe the discovery of two clinical candidate IRAK4 inhibitors, BAY1834845 (zabedosertib) and BAY1830839, starting from a high-throughput screening hit derived from Bayer's compound library. By exploiting binding site features distinct to IRAK4 using an in-house docking model, liabilities of the original hit could surprisingly be overcome to confer both candidates with a unique combination of good potency and selectivity. Favorable DMPK profiles and activity in animal inflammation models led to the selection of these two compounds for clinical development in patients.
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Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wengner, A.M., Guimond, N., Thaler, T., Platzek, J., Ewerspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.
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Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839.,Bothe U, Gunther J, Nubbemeyer R, Siebeneicher H, Ring S, Bomer U, Peters M, Rausch A, Denner K, Himmel H, Sutter A, Terebesi I, Lange M, Wengner AM, Guimond N, Thaler T, Platzek J, Eberspacher U, Schafer M, Steuber H, Zollner TM, Steinmeyer A, Schmidt N J Med Chem. 2024 Jan 25;67(2):1225-1242. doi: 10.1021/acs.jmedchem.3c01714. Epub , 2024 Jan 16. PMID:38228402<ref>PMID:38228402</ref>
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Description: Discovery of IRAK4 Inhibitor 40
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Lange, M]]
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<div class="pdbe-citations 8br6" style="background-color:#fffaf0;"></div>
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[[Category: Gunther, J]]
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== References ==
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[[Category: Guimond, N]]
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<references/>
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[[Category: Steinmeyer, A]]
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__TOC__
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[[Category: Terebesi, I]]
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</StructureSection>
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[[Category: Denner, K]]
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[[Category: Homo sapiens]]
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[[Category: Peters, M]]
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[[Category: Large Structures]]
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[[Category: Thaler, T]]
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[[Category: Boemer U]]
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[[Category: Sutter, A]]
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[[Category: Bothe U]]
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[[Category: Schafer, M]]
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[[Category: Denner K]]
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[[Category: Zollner, T.M]]
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[[Category: Ewerspaecher U]]
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[[Category: Bothe, U]]
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[[Category: Guimond N]]
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[[Category: Platzek, J]]
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[[Category: Gunther J]]
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[[Category: Ring, S]]
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[[Category: Himmel H]]
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[[Category: Steuber, H]]
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[[Category: Lange M]]
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[[Category: Wengner, A.M]]
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[[Category: Nubbemeyer R]]
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[[Category: Schmidt, N]]
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[[Category: Peters M]]
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[[Category: Himmel, H]]
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[[Category: Platzek J]]
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[[Category: Siebeneicher, H]]
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[[Category: Ring S]]
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[[Category: Ewerspaecher, U]]
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[[Category: Schafer M]]
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[[Category: Boemer, U]]
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[[Category: Schmidt N]]
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[[Category: Nubbemeyer, R]]
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[[Category: Siebeneicher H]]
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[[Category: Steinmeyer A]]
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[[Category: Steuber H]]
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[[Category: Sutter A]]
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[[Category: Terebesi I]]
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[[Category: Thaler T]]
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[[Category: Wengner AM]]
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[[Category: Zollner TM]]

Current revision

Discovery of IRAK4 Inhibitor 40

PDB ID 8br6

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