7chm: Difference between revisions

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New page: '''Unreleased structure''' The entry 7chm is ON HOLD Authors: Kim, H.L., Cho, H.Y., Park, Y.W., Lee, Y.H., Son, J.B., Ko, E.H., Choi, H.G., Kim, N.D. Description: Crystal structure of ...
 
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'''Unreleased structure'''


The entry 7chm is ON HOLD
==Crystal structure of TTK kinase domain in complex with compound 8==
<StructureSection load='7chm' size='340' side='right'caption='[[7chm]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CHM 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FZF:4-(cyclohexylamino)-2-[(2-methoxy-4-morpholin-4-ylcarbonyl-phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile'>FZF</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=7chm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7chm OCA], [https://pdbe.org/7chm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7chm RCSB], [https://www.ebi.ac.uk/pdbsum/7chm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7chm 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.


Authors: Kim, H.L., Cho, H.Y., Park, Y.W., Lee, Y.H., Son, J.B., Ko, E.H., Choi, H.G., Kim, N.D.
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>


Description: Crystal structure of TTK kinase domain in complex with compound 8
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Kim, H.L]]
<div class="pdbe-citations 7chm" style="background-color:#fffaf0;"></div>
[[Category: Ko, E.H]]
 
[[Category: Choi, H.G]]
==See Also==
[[Category: Kim, N.D]]
*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
[[Category: Cho, H.Y]]
== References ==
[[Category: Park, Y.W]]
<references/>
[[Category: Lee, Y.H]]
__TOC__
[[Category: Son, J.B]]
</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]]

Latest revision as of 13:55, 23 October 2024

Crystal structure of TTK kinase domain in complex with compound 8Crystal structure of TTK kinase domain in complex with compound 8

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.65Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Lee Y, Kim H, Kim H, Cho HY, Jee JG, Seo KA, Son JB, Ko E, Choi HG, Kim ND, Kim I. 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. J Med Chem. 2021 May 4. doi: 10.1021/acs.jmedchem.1c00542. PMID:33942608 doi:http://dx.doi.org/10.1021/acs.jmedchem.1c00542

7chm, resolution 2.65Å

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