3o9l: Difference between revisions
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==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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9L FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | ||
[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://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> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3g6z|3g6z]], [[3oag|3oag]], [[3oad|3oad]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REN ([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/Renin Renin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.15 3.4.23.15] </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=3o9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o9l RCSB], [http://www.ebi.ac.uk/pdbsum/3o9l PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/RENI_HUMAN RENI_HUMAN]] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:[http://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:[http://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 == | |||
[[http://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> | |||
==See Also== | ==See Also== | ||
*[[Renin|Renin]] | *[[Renin|Renin]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Renin]] | [[Category: Renin]] | ||
[[Category: Bezencon, O | [[Category: Bezencon, O]] | ||
[[Category: Bur, D | [[Category: Bur, D]] | ||
[[Category: Corminboeuf, O | [[Category: Corminboeuf, O]] | ||
[[Category: Grisostomi, C | [[Category: Grisostomi, C]] | ||
[[Category: Hess, P | [[Category: Hess, P]] | ||
[[Category: Prade, L | [[Category: Prade, L]] | ||
[[Category: Remen, L | [[Category: Remen, L]] | ||
[[Category: Richard-Bildstein, S | [[Category: Richard-Bildstein, S]] | ||
[[Category: Strickner, P | [[Category: Strickner, P]] | ||
[[Category: Treiber, A | [[Category: Treiber, A]] | ||
[[Category: Blood]] | [[Category: Blood]] | ||
[[Category: Glycosilation]] | [[Category: Glycosilation]] | ||
