7kie
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
==Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 3== | ==Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 3== | ||
| - | <StructureSection load='7kie' size='340' side='right'caption='[[7kie]]' scene=''> | + | <StructureSection load='7kie' size='340' side='right'caption='[[7kie]], [[Resolution|resolution]] 2.47Å' 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=7KIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIE FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIE 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=7kie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kie OCA], [https://pdbe.org/7kie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kie RCSB], [https://www.ebi.ac.uk/pdbsum/7kie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kie 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]] 2.47Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=WF7:N-{4-[(E)-2-{4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}ethenyl]phenyl}prop-2-enamide'>WF7</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=7kie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kie OCA], [https://pdbe.org/7kie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kie RCSB], [https://www.ebi.ac.uk/pdbsum/7kie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kie ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties. | ||
| + | |||
| + | Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3.,Brawn RA, Cook A, Omoto K, Ke J, Karr C, Colombo F, Virrankoski M, Prajapati S, Reynolds D, Bolduc DM, Nguyen TV, Gee P, Borrelli D, Caleb B, Yao S, Irwin S, Larsen NA, Selvaraj A, Zhao X, Ioannidis S ACS Med Chem Lett. 2020 Dec 2;12(1):93-98. doi: 10.1021/acsmedchemlett.0c00517., eCollection 2021 Jan 14. PMID:33488969<ref>PMID:33488969</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kie" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Fibroblast growth factor receptor 3D receptor|Fibroblast growth factor receptor 3D receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 3
| |||||||||||
