7aj5
From Proteopedia
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==Structure of DYRK1A in complex with compound 10== | ==Structure of DYRK1A in complex with compound 10== | ||
| - | <StructureSection load='7aj5' size='340' side='right'caption='[[7aj5]]' scene=''> | + | <StructureSection load='7aj5' size='340' side='right'caption='[[7aj5]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AJ5 FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AJ5 FirstGlance]. <br> | ||
| - | </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=7aj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aj5 OCA], [https://pdbe.org/7aj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aj5 RCSB], [https://www.ebi.ac.uk/pdbsum/7aj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aj5 ProSAT]</span></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]] 2Å</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=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=RHW:4-(1-benzofuran-5-yl)pyridine-2,6-diamine'>RHW</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=7aj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aj5 OCA], [https://pdbe.org/7aj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aj5 RCSB], [https://www.ebi.ac.uk/pdbsum/7aj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aj5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The kinase DYRK1A is an attractive target for drug discovery programs due to its implication in multiple diseases. Through a fragment screen, we identified a simple biaryl compound that is bound to the DYRK1A ATP site with very high efficiency, although with limited selectivity. Structure-guided optimization cycles enabled us to convert this fragment hit into potent and selective DYRK1A inhibitors. Exploiting the structural differences in DYRK1A and its close homologue DYRK2, we were able to fine-tune the selectivity of our inhibitors. Our best compounds potently inhibited DYRK1A in the cell culture and in vivo and demonstrated drug-like properties. The inhibition of DYRK1A in vivo translated into dose-dependent tumor growth inhibition in a model of ovarian carcinoma. | ||
| + | |||
| + | Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors.,Weber C, Sipos M, Paczal A, Balint B, Kun V, Foloppe N, Dokurno P, Massey AJ, Walmsley DL, Hubbard RE, Murray J, Benwell K, Edmonds T, Demarles D, Bruno A, Burbridge M, Cruzalegui F, Kotschy A J Med Chem. 2021 May 12. doi: 10.1021/acs.jmedchem.1c00023. PMID:33975430<ref>PMID:33975430</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7aj5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of DYRK1A in complex with compound 10
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