3o9l
From Proteopedia
(Difference between revisions)
| (11 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Design and optimisation of new piperidines as renin inhibitors== | |
| + | <StructureSection load='3o9l' size='340' side='right'caption='[[3o9l]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3o9l]] is a 4 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=3O9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O9L 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]] 2.4Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LPN:(3R,4S)-N-[2-CHLORO-5-(3-METHOXYPROPYL)BENZYL]-N-CYCLOPROPYL-4-{4-[2-(2,6-DICHLORO-4-METHYLPHENOXY)ETHOXY]PHENYL}PIPERIDINE-3-CARBOXAMIDE'>LPN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3o9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9l OCA], [https://pdbe.org/3o9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o9l RCSB], [https://www.ebi.ac.uk/pdbsum/3o9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o9l ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[https://omim.org/entry/267430 267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).<ref>PMID:16116425</ref> Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:[https://omim.org/entry/613092 613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.<ref>PMID:19664745</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN] Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The discovery of a new series of piperidine-based renin inhibitors is described herein. SAR optimization upon the P3 renin sub-pocket is described, leading to the discovery of 9 and 41, two bioavailable renin inhibitors orally active at low doses in a transgenic rat model of hypertension. | ||
| - | + | Design and optimization of new piperidines as renin inhibitors.,Corminboeuf O, Bezencon O, Grisostomi C, Remen L, Richard-Bildstein S, Bur D, Prade L, Hess P, Strickner P, Fischli W, Steiner B, Treiber A Bioorg Med Chem Lett. 2010 Nov 1;20(21):6286-90. Epub 2010 Aug 22. PMID:20843686<ref>PMID:20843686</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3o9l" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Renin|Renin]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bezencon O]] | ||
| + | [[Category: Bur D]] | ||
| + | [[Category: Corminboeuf O]] | ||
| + | [[Category: Grisostomi C]] | ||
| + | [[Category: Hess P]] | ||
| + | [[Category: Prade L]] | ||
| + | [[Category: Remen L]] | ||
| + | [[Category: Richard-Bildstein S]] | ||
| + | [[Category: Strickner P]] | ||
| + | [[Category: Treiber A]] | ||
Current revision
Design and optimisation of new piperidines as renin inhibitors
| |||||||||||
Categories: Homo sapiens | Large Structures | Bezencon O | Bur D | Corminboeuf O | Grisostomi C | Hess P | Prade L | Remen L | Richard-Bildstein S | Strickner P | Treiber A
