View source for 7cil


==Crystal structure of TTK kinase domain in complex with compound 7==
<StructureSection load='7cil' size='340' side='right'caption='[[7cil]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CIL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FZR:4-(cyclohexylamino)-2-[(1-methylpyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile'>FZR</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=7cil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cil OCA], [https://pdbe.org/7cil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cil RCSB], [https://www.ebi.ac.uk/pdbsum/7cil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cil ProSAT]</span></td></tr>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7cil" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Cho HY]]
[[Category: Choi HG]]
[[Category: Kim HL]]
[[Category: Kim ND]]
[[Category: Ko EH]]
[[Category: Lee YH]]
[[Category: Park YW]]
[[Category: Son JB]]