7ajy
From Proteopedia
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==Structure of DYRK1A in complex with compound 51== | ==Structure of DYRK1A in complex with compound 51== | ||
| - | <StructureSection load='7ajy' size='340' side='right'caption='[[7ajy]]' scene=''> | + | <StructureSection load='7ajy' size='340' side='right'caption='[[7ajy]], [[Resolution|resolution]] 2.20Å' 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=7AJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AJY FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AJY 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=7ajy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ajy OCA], [https://pdbe.org/7ajy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ajy RCSB], [https://www.ebi.ac.uk/pdbsum/7ajy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ajy 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]] 2.2Å</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=RKZ:4-[2-methyl-3-[(2~{R})-2-phenoxypropyl]imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine'>RKZ</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=7ajy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ajy OCA], [https://pdbe.org/7ajy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ajy RCSB], [https://www.ebi.ac.uk/pdbsum/7ajy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ajy 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 7ajy" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of DYRK1A in complex with compound 51
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