6y5m: Difference between revisions
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New page: '''Unreleased structure''' The entry 6y5m is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures |
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==Crystal structure of mouse Autotaxin in complex with compound 1a== | |||
<StructureSection load='6y5m' size='340' side='right'caption='[[6y5m]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y5M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y5M 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]] 2.011Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=O9W:(~{E})-3-[4-chloranyl-2-[(5-methyl-1,2,3,4-tetrazol-2-yl)methyl]phenyl]-1-[(2~{R})-4-[(4-fluorophenyl)methyl]-2-methyl-piperazin-1-yl]prop-2-en-1-one'>O9W</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6y5m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y5m OCA], [https://pdbe.org/6y5m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y5m RCSB], [https://www.ebi.ac.uk/pdbsum/6y5m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y5m ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of inhibitors of Autotaxin (ATX) have been developed from a high throughput screening hit, 1a, which shows an alternative binding mode to known catalytic site inhibitors. Selectivity over the hERG channel and microsomal clearance were dependent on the lipophilicity of the compounds, and this was optimised by reduction of clogD whilst maintaining high affinity ATX inhibition. Compound 15a shows good oral exposure, and concentration dependent inhibition of formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic (PK/PD) experiments. | |||
Development of autotaxin inhibitors: A series of tetrazole cinnamides.,Thomson CG, Le Grand D, Dowling M, Beattie D, Elphick L, Faller M, Freeman M, Hardaker E, Head V, Hemmig R, Hill J, Lister A, Pascoe D, Rieffel S, Shrestha B, Steward O, Zink F Bioorg Med Chem Lett. 2020 Nov 4:127663. doi: 10.1016/j.bmcl.2020.127663. PMID:33160025<ref>PMID:33160025</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6y5m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Faller M]] | |||
[[Category: Zink F]] | |||
Latest revision as of 13:44, 23 October 2024
Crystal structure of mouse Autotaxin in complex with compound 1aCrystal structure of mouse Autotaxin in complex with compound 1a
Structural highlights
Publication Abstract from PubMedA series of inhibitors of Autotaxin (ATX) have been developed from a high throughput screening hit, 1a, which shows an alternative binding mode to known catalytic site inhibitors. Selectivity over the hERG channel and microsomal clearance were dependent on the lipophilicity of the compounds, and this was optimised by reduction of clogD whilst maintaining high affinity ATX inhibition. Compound 15a shows good oral exposure, and concentration dependent inhibition of formation of LPA in vivo, as shown in pharmacokinetic-pharmacodynamic (PK/PD) experiments. Development of autotaxin inhibitors: A series of tetrazole cinnamides.,Thomson CG, Le Grand D, Dowling M, Beattie D, Elphick L, Faller M, Freeman M, Hardaker E, Head V, Hemmig R, Hill J, Lister A, Pascoe D, Rieffel S, Shrestha B, Steward O, Zink F Bioorg Med Chem Lett. 2020 Nov 4:127663. doi: 10.1016/j.bmcl.2020.127663. PMID:33160025[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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