2fvc: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31647 Hepatitis C virus subtype 1b]) | |GENE= NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31647 Hepatitis C virus subtype 1b]) | ||
|DOMAIN= | |||
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fvc OCA], [http://www.ebi.ac.uk/pdbsum/2fvc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fvc RCSB]</span> | |||
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[[Category: Singh, O.]] | [[Category: Singh, O.]] | ||
[[Category: Wonacott, A.]] | [[Category: Wonacott, A.]] | ||
[[Category: hcv polymerase]] | [[Category: hcv polymerase]] | ||
[[Category: thiadiazin inhibitor]] | [[Category: thiadiazin inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:08:07 2008'' | ||
Revision as of 03:08, 31 March 2008
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| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | NS5B (Hepatitis C virus subtype 1b) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of NS5B BK strain (delta 24) in complex with a 3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinone
OverviewOverview
Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.
About this StructureAbout this Structure
2FVC is a Single protein structure of sequence from Hepatitis c virus subtype 1b. Full crystallographic information is available from OCA.
ReferenceReference
3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones , potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase., Tedesco R, Shaw AN, Bambal R, Chai D, Concha NO, Darcy MG, Dhanak D, Fitch DM, Gates A, Gerhardt WG, Halegoua DL, Han C, Hofmann GA, Johnston VK, Kaura AC, Liu N, Keenan RM, Lin-Goerke J, Sarisky RT, Wiggall KJ, Zimmerman MN, Duffy KJ, J Med Chem. 2006 Feb 9;49(3):971-83. PMID:16451063
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