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[[ | ==I. Novel HCV NS5B Polymerase Inhibitors: Discovery of Indole 2- Carboxylic Acids with C3-Heterocycles== | ||
<StructureSection load='3skh' size='340' side='right' caption='[[3skh]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3skh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SKH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=058:1-BENZYL-5-CHLORO-3-(2-FLUOROPHENYL)-1H-INDOLE-2-CARBOXYLIC+ACID'>058</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ska|3ska]], [[3ske|3ske]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=3skh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3skh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3skh RCSB], [http://www.ebi.ac.uk/pdbsum/3skh PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9muM, replicon EC(50)>100muM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032muM, replicon EC(50)=1.4muM) and 7r (NS5B IC(50)=0.017muM, replicon EC(50)=0.3muM) with improved enzyme and replicon activity. | |||
I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles.,Anilkumar GN, Lesburg CA, Selyutin O, Rosenblum SB, Zeng Q, Jiang Y, Chan TY, Pu H, Vaccaro H, Wang L, Bennett F, Chen KX, Duca J, Gavalas S, Huang Y, Pinto P, Sannigrahi M, Velazquez F, Venkatraman S, Vibulbhan B, Agrawal S, Butkiewicz N, Feld B, Ferrari E, He Z, Jiang CK, Palermo RE, McMonagle P, Huang HC, Shih NY, Njoroge G, Kozlowski JA Bioorg Med Chem Lett. 2011 Sep 15;21(18):5336-41. Epub 2011 Jul 19. PMID:21840715<ref>PMID:21840715</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[RNA polymerase|RNA polymerase]] | *[[RNA polymerase|RNA polymerase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
[[Category: Viruses]] | [[Category: Viruses]] | ||
[[Category: Anilkumar, G N | [[Category: Anilkumar, G N]] | ||
[[Category: Lesburg, C A | [[Category: Lesburg, C A]] | ||
[[Category: Rna-dependent rna polymerase]] | [[Category: Rna-dependent rna polymerase]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 14:11, 9 December 2014
I. Novel HCV NS5B Polymerase Inhibitors: Discovery of Indole 2- Carboxylic Acids with C3-HeterocyclesI. Novel HCV NS5B Polymerase Inhibitors: Discovery of Indole 2- Carboxylic Acids with C3-Heterocycles
Structural highlights
Publication Abstract from PubMedSAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9muM, replicon EC(50)>100muM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032muM, replicon EC(50)=1.4muM) and 7r (NS5B IC(50)=0.017muM, replicon EC(50)=0.3muM) with improved enzyme and replicon activity. I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles.,Anilkumar GN, Lesburg CA, Selyutin O, Rosenblum SB, Zeng Q, Jiang Y, Chan TY, Pu H, Vaccaro H, Wang L, Bennett F, Chen KX, Duca J, Gavalas S, Huang Y, Pinto P, Sannigrahi M, Velazquez F, Venkatraman S, Vibulbhan B, Agrawal S, Butkiewicz N, Feld B, Ferrari E, He Z, Jiang CK, Palermo RE, McMonagle P, Huang HC, Shih NY, Njoroge G, Kozlowski JA Bioorg Med Chem Lett. 2011 Sep 15;21(18):5336-41. Epub 2011 Jul 19. PMID:21840715[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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