5ei2: Difference between revisions
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<StructureSection load='5ei2' size='340' side='right' caption='[[5ei2]], [[Resolution|resolution]] 2.67Å' scene=''> | <StructureSection load='5ei2' size='340' side='right' caption='[[5ei2]], [[Resolution|resolution]] 2.67Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ei2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EI2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ei2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EI2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5O7:~{N}-(2,4-DIMETHOXYPHENYL)-8-(1-METHYLPYRAZOL-4-YL)PYRIDO[3,4-D]PYRIMIDIN-2-AMINE'>5O7</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5O7:~{N}-(2,4-DIMETHOXYPHENYL)-8-(1-METHYLPYRAZOL-4-YL)PYRIDO[3,4-D]PYRIMIDIN-2-AMINE'>5O7</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eh0|5eh0]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eh0|5eh0]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTK, MPS1, MPS1L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr> | ||
<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=5ei2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei2 OCA], [http://pdbe.org/5ei2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ei2 RCSB], [http://www.ebi.ac.uk/pdbsum/5ei2 PDBsum]</span></td></tr> | <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=5ei2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ei2 OCA], [http://pdbe.org/5ei2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ei2 RCSB], [http://www.ebi.ac.uk/pdbsum/5ei2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ei2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Dual-specificity kinase]] | [[Category: Dual-specificity kinase]] | ||
[[Category: Human]] | |||
[[Category: Baker, R]] | [[Category: Baker, R]] | ||
[[Category: Blagg, J]] | [[Category: Blagg, J]] | ||
Revision as of 15:33, 16 November 2017
Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle kinase 1 (MPS1) Using a Structure-Based Hydridization ApproachRapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle kinase 1 (MPS1) Using a Structure-Based Hydridization Approach
Structural highlights
Function[TTK_HUMAN] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.[1] Publication Abstract from PubMedMonopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft model. Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.,Innocenti P, Woodward HL, Solanki S, Naud S, Westwood IM, Cronin N, Hayes A, Roberts J, Henley AT, Baker R, Faisal A, Mak GW, Box G, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Matijssen B, Burke R, van Montfort RL, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S J Med Chem. 2016 Apr 28;59(8):3671-88. doi: 10.1021/acs.jmedchem.5b01811. Epub, 2016 Apr 7. PMID:27055065[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Dual-specificity kinase
- Human
- Baker, R
- Blagg, J
- Box, G
- Brandon, A De Haven
- Burke, R
- Cronin, N
- Eccles, S A
- Faisal, A
- Fee, L O
- Hayes, A
- Henley, A T
- Hoelder, S
- Innocenti, P
- Linardopoulos, S
- Mak, G
- Montfort, R L.M van
- Naud, N
- Raymaud, F I
- Roberts, J
- Saville, J
- Schmitt, J
- Solanki, S
- Valenti, M
- Westwood, I M
- Woodward, H L
- Transferase