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[[ | ==Catalytic domain of human phosphodiesterase 4b2b in complex with a 5-heterocycle pyrazolopyridine inhibitor== | ||
<StructureSection load='3o56' size='340' side='right' caption='[[3o56]], [[Resolution|resolution]] 2.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o56]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O56 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ARS:ARSENIC'>ARS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZG1:1-ETHYL-5-[3-(2-OXO-2-PYRROLIDIN-1-YLETHYL)-1,2,4-OXADIAZOL-5-YL]-N-(TETRAHYDRO-2H-PYRAN-4-YL)-1H-PYRAZOLO[3,4-B]PYRIDIN-4-AMINE'>ZG1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d3p|3d3p]], [[3o57|3o57]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE4B, DPDE4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3',5'-cyclic-nucleotide_phosphodiesterase 3',5'-cyclic-nucleotide phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.17 3.1.4.17] </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=3o56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o56 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o56 RCSB], [http://www.ebi.ac.uk/pdbsum/3o56 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-alpha production from isolated human peripheral blood mononuclear cells. | |||
Pyrazolopyridines as potent PDE4B inhibitors: 5-heterocycle SAR.,Mitchell CJ, Ballantine SP, Coe DM, Cook CM, Delves CJ, Dowle MD, Edlin CD, Hamblin JN, Holman S, Johnson MR, Jones PS, Keeling SE, Kranz M, Lindvall M, Lucas FS, Neu M, Solanke YE, Somers DO, Trivedi NA, Wiseman JO Bioorg Med Chem Lett. 2010 Oct 1;20(19):5803-6. Epub 2010 Aug 5. PMID:20732811<ref>PMID:20732811</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase|Phosphodiesterase]] | *[[Phosphodiesterase|Phosphodiesterase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | [[Category: 3',5'-cyclic-nucleotide phosphodiesterase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Neu, M | [[Category: Neu, M]] | ||
[[Category: Somers, D O | [[Category: Somers, D O]] | ||
[[Category: Camp binding]] | [[Category: Camp binding]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 13:45, 9 December 2014
Catalytic domain of human phosphodiesterase 4b2b in complex with a 5-heterocycle pyrazolopyridine inhibitorCatalytic domain of human phosphodiesterase 4b2b in complex with a 5-heterocycle pyrazolopyridine inhibitor
Structural highlights
Publication Abstract from PubMedFollowing the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-alpha production from isolated human peripheral blood mononuclear cells. Pyrazolopyridines as potent PDE4B inhibitors: 5-heterocycle SAR.,Mitchell CJ, Ballantine SP, Coe DM, Cook CM, Delves CJ, Dowle MD, Edlin CD, Hamblin JN, Holman S, Johnson MR, Jones PS, Keeling SE, Kranz M, Lindvall M, Lucas FS, Neu M, Solanke YE, Somers DO, Trivedi NA, Wiseman JO Bioorg Med Chem Lett. 2010 Oct 1;20(19):5803-6. Epub 2010 Aug 5. PMID:20732811[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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