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==Crystal structure of TTK kinase domain in complex with compound 19== | ==Crystal structure of TTK kinase domain in complex with compound 19== | ||
<StructureSection load='7clh' size='340' side='right'caption='[[7clh]]' scene=''> | <StructureSection load='7clh' size='340' side='right'caption='[[7clh]], [[Resolution|resolution]] 2.90Å' 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=7CLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLH FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CLH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CLH 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=7clh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7clh OCA], [https://pdbe.org/7clh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7clh RCSB], [https://www.ebi.ac.uk/pdbsum/7clh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7clh 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]] 2.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G5C:2-[[2-methoxy-4-(2-oxidanylidenepyrrolidin-1-yl)phenyl]amino]-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile'>G5C</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=7clh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7clh OCA], [https://pdbe.org/7clh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7clh RCSB], [https://www.ebi.ac.uk/pdbsum/7clh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7clh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Triple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) is an apical dual-specificity protein kinase that is over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on a 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) is shown to effectively mitigate human TNBC cell proliferation. | |||
X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.,Lee Y, Kim H, Kim H, Cho HY, Jee JG, Seo KA, Son JB, Ko E, Choi HG, Kim ND, Kim I J Med Chem. 2021 May 4. doi: 10.1021/acs.jmedchem.1c00542. PMID:33942608<ref>PMID:33942608</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7clh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 13:55, 23 October 2024
Crystal structure of TTK kinase domain in complex with compound 19Crystal structure of TTK kinase domain in complex with compound 19
Structural highlights
Publication Abstract from PubMedTriple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) is an apical dual-specificity protein kinase that is over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on a 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) is shown to effectively mitigate human TNBC cell proliferation. X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor.,Lee Y, Kim H, Kim H, Cho HY, Jee JG, Seo KA, Son JB, Ko E, Choi HG, Kim ND, Kim I J Med Chem. 2021 May 4. doi: 10.1021/acs.jmedchem.1c00542. PMID:33942608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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