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3oag

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Revision as of 11:59, 5 August 2016

Design and optimization of new piperidines as renin inhibitors

Structural highlights

3oag is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3oad, 3oec, 3o9l
Gene:	REN (HUMAN)
Activity:	Renin, with EC number 3.4.23.15
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[RENI_HUMAN] Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM: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).^[1] Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia.^[2]

Function

[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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet. 2005 Sep;37(9):964-8. Epub 2005 Aug 14. PMID:16116425 doi:ng1623
↑ Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, Baresova V, Sikora J, Blazkova H, Zivny J, Ivanek R, Stranecky V, Sovova J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gubler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009 Aug;85(2):204-13. Epub 2009 Aug 6. PMID:19664745 doi:10.1016/j.ajhg.2009.07.010
↑ 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. Design and optimization of new piperidines as renin inhibitors. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6286-90. Epub 2010 Aug 22. PMID:20843686 doi:10.1016/j.bmcl.2010.08.086

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3oag"

@@ Line 1: / Line 1: @@
 ==Design and optimization of new piperidines as renin inhibitors==
 <StructureSection load='3oag' size='340' side='right' caption='[[3oag]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3oag]] 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=3OAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3oag]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LPQ:(3R,4S)-N-{2-CHLORO-5-[(CYCLOPROPYLAMINO)METHYL]BENZYL}-N-CYCLOPROPYL-4-{6-[2-(2,6-DICHLORO-4-METHYLPHENOXY)ETHOXY]PYRIDIN-3-YL}PIPERIDINE-3-CARBOXAMIDE'>LPQ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3oad|3oad]], [[3oec|3oec]], [[3o9l|3o9l]]</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='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 HUMAN])</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=3oag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oag OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oag RCSB], [http://www.ebi.ac.uk/pdbsum/3oag PDBsum]</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=3oag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oag OCA], [http://pdbe.org/3oag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3oag RCSB], [http://www.ebi.ac.uk/pdbsum/3oag PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3oag ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3oag" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 30: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Renin]]
 [[Category: Prade, L]]

3oag

From Proteopedia

Revision as of 11:59, 5 August 2016

Design and optimization of new piperidines as renin inhibitors

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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