5eak

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==Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties==
==Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties==
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<StructureSection load='5eak' size='340' side='right' caption='[[5eak]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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<StructureSection load='5eak' size='340' side='right'caption='[[5eak]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5eak]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EAK FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5eak]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EAK FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=24R:N-[(1S,2R)-2-AMINOCYCLOHEXYL]-4-[6-(1-METHYL-1H-PYRAZOL-4-YL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]THIOPHENE-2-CARBOXAMIDE'>24R</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eak OCA], [http://pdbe.org/5eak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eak RCSB], [http://www.ebi.ac.uk/pdbsum/5eak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eak ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=24R:N-[(1S,2R)-2-AMINOCYCLOHEXYL]-4-[6-(1-METHYL-1H-PYRAZOL-4-YL)PYRAZOLO[1,5-A]PYRIMIDIN-3-YL]THIOPHENE-2-CARBOXAMIDE'>24R</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eak OCA], [https://pdbe.org/5eak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eak RCSB], [https://www.ebi.ac.uk/pdbsum/5eak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eak ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/MARK2_HUMAN MARK2_HUMAN]
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Inhibition of microtubule affinity regulating kinase (MARK) represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. This manuscript outlines efforts to optimize a pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in potency, physical properties and attributes amenable to CNS penetration. A unique cylcyclohexyldiamine scaffold was identified that led to remarkable improvements in potency, opening up opportunities to reduce MW, Pgp efflux and improve pharmacokinetic properties while also conferring improved solubility.
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Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties.,Sloman DL, Noucti N, Altman MD, Chen D, Mislak AC, Szewczak A, Hayashi M, Warren L, Dellovade T, Wu Z, Marcus J, Walker D, Su HP, Edavettal SC, Munshi S, Hutton M, Nuthall H, Stanton MG Bioorg Med Chem Lett. 2016 Sep 1;26(17):4362-6. doi: 10.1016/j.bmcl.2016.02.003. , Epub 2016 Feb 6. PMID:27491711<ref>PMID:27491711</ref>
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==See Also==
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5eak" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Su, H P]]
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[[Category: Homo sapiens]]
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[[Category: Catalytic domain]]
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[[Category: Large Structures]]
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[[Category: Kinase inhibitor]]
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[[Category: Su HP]]
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[[Category: Protein-serine-threonine kinase]]
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[[Category: Serine-threonine kinase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties

PDB ID 5eak

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