6xz8: Difference between revisions
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<StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='6xz8' size='340' side='right'caption='[[6xz8]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XZ8 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]] 3Å</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]] 3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O4T:~{N}-[(1~{R})-1-[5-(6-chloranyl-1,1-dimethyl-3-oxidanylidene-isoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide'>O4T</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=O4T:~{N}-[(1~{R})-1-[5-(6-chloranyl-1,1-dimethyl-3-oxidanylidene-isoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide'>O4T</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=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [https://pdbe.org/6xz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [https://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 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=6xz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xz8 OCA], [https://pdbe.org/6xz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xz8 RCSB], [https://www.ebi.ac.uk/pdbsum/6xz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xz8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | |||
Aldosterone synthase (CYP11B2) inhibitors were explored in recent years as an alternative therapeutic option to MR antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including heart, vasculature, kidney, and CNS. A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 44, in an in vivo cynomolgus monkey acute ACTH challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1. | |||
Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.,Liu Y, Wu J, Zhou M, Chen W, Li D, Wang ZG, Hornsperger B, Aebi JD, Marki HP, Kuhn B, Wang L, Kuglstatter A, Benz J, Muller S, Hochstrasser R, Ottaviani G, Xin J, Kirchner S, Mohr S, Verry P, Riboulet W, Shen HC, Mayweg AV, Amrein K, Tan X J Med Chem. 2020 Jun 12. doi: 10.1021/acs.jmedchem.0c00233. PMID:32530624<ref>PMID:32530624</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6xz8" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Benz J]] | [[Category: Benz J]] | ||
[[Category: Joseph C]] | [[Category: Joseph C]] | ||
[[Category: Kuglstatter A]] | [[Category: Kuglstatter A]] | ||
Latest revision as of 18:41, 8 September 2026
Structure of aldosterone synthase (CYP11B2) in complex with N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxo-isoindolin-2-yl)-3-pyridyl]ethyl]methanesulfonamide
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