4pm0: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4pm0]] is a 1 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=4PM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PM0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4pm0]] is a 1 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=4PM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PM0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32V:2-(CYCLOPENTYLAMINO)-3-ETHYL-7-ETHYNYLTHIENO[3,2-D]PYRIMIDIN-4(3H)-ONE'>32V</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=32V:2-(CYCLOPENTYLAMINO)-3-ETHYL-7-ETHYNYLTHIENO[3,2-D]PYRIMIDIN-4(3H)-ONE'>32V</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4pm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pm0 OCA], [https://pdbe.org/4pm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pm0 RCSB], [https://www.ebi.ac.uk/pdbsum/4pm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pm0 ProSAT]</span></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=4pm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pm0 OCA], [https://pdbe.org/4pm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pm0 RCSB], [https://www.ebi.ac.uk/pdbsum/4pm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pm0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 18:00, 8 November 2023
PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivativePDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative
Structural highlights
FunctionPDE7A_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.[1] Publication Abstract from PubMedThe discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy. Discovery of 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one Derivatives as a New Series of Potent Phosphodiesterase 7 Inhibitors.,Kawai K, Endo Y, Asano T, Amano S, Sawada K, Ueo N, Takahashi N, Sonoda Y, Nagai M, Kamei N, Nagata N J Med Chem. 2014 Nov 19. PMID:25383422[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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