5u7r: Difference between revisions

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-'''Unreleased structure'''
-The entry 5u7r is ON HOLD  until Paper Publication
+==Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative Pharmacophore Model: Synthesis and Biological Evaluation of 2,3-Dihydrothieno[3,2-d]pyrimidin-4(1H)-ones==
+<StructureSection load='5u7r' size='340' side='right' caption='[[5u7r]], [[Resolution|resolution]] 3.33&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5u7r]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U7R FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=81G:(1S,4S)-4-(4-FLUOROPHENYL)-4-HYDROXY-6-(5-METHYL-1H-PYRAZOL-4-YL)-1H-SPIRO[CYCLOHEXANE-1,2-THIENO[3,2-D]PYRIMIDIN]-4(3H)-ONE'>81G</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u7q|5u7q]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5u7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7r OCA], [http://pdbe.org/5u7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u7r RCSB], [http://www.ebi.ac.uk/pdbsum/5u7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7r ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ROCK2_HUMAN ROCK2_HUMAN]] Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus.<ref>PMID:10579722</ref> <ref>PMID:15699075</ref> <ref>PMID:16574662</ref> <ref>PMID:17015463</ref> <ref>PMID:19131646</ref> <ref>PMID:19997641</ref> <ref>PMID:21084279</ref> <ref>PMID:21147781</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures.
-Authors: Hoffman, I.D., Skene, R.J.
+Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones.,Kurasawa O, Oguro Y, Miyazaki T, Homma M, Mori K, Iwai K, Hara H, Skene R, Hoffman I, Ohashi A, Yoshida S, Ishikawa T, Cho N Bioorg Med Chem. 2017 Apr 1;25(7):2133-2147. doi: 10.1016/j.bmc.2017.02.021. Epub, 2017 Feb 16. PMID:28284870<ref>PMID:28284870</ref>
-Description: Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative Pharmacophore Model: Synthesis and Biological Evaluation of 2,3-Dihydrothieno[3,2-d]pyrimidin-4(1H)-ones
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Hoffman, I.D]]
+<div class="pdbe-citations 5u7r" style="background-color:#fffaf0;"></div>
-[[Category: Skene, R.J]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Hoffman, I D]]
+[[Category: Skene, R J]]
+[[Category: Apo-protein]]
+[[Category: Serine/threonine kinase]]
+[[Category: Transferase]]