3G86

Hepatitis C virus polymerase NS5B (BK 1-570) with thiazine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure-activity relationships of benzothiazine-substituted quinolinediones

de Vicente, J.Hendricks, R.T.Smith, D.B.Fell, J.B.Fischer, J.Spencer, S.R.Stengel, P.J.Mohr, P.Robinson, J.E.Blake, J.F.Hilgenkamp, R.K.Yee, C.Adjabeng, G.Elworthy, T.R.Tracy, J.Chin, E.Li, J.Wang, B.Bamberg, J.T.Stephenson, R.Oshiro, C.Harris, S.F.Ghate, M.Leveque, V.Najera, I.Le Pogam, S.Rajyaguru, S.Ao-Ieong, G.Alexandrova, L.Larrabee, S.Brandl, M.Briggs, A.Sukhtankar, S.Farrell, R.Xu, B.

(2009) Bioorg Med Chem Lett 19: 3642-3646

  • DOI: https://doi.org/10.1016/j.bmcl.2009.05.004
  • Primary Citation of Related Structures:  
    3G86

  • PubMed Abstract: 

    A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.


  • Organizational Affiliation

    Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. javier.devicente@roche.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
576Hepatitis C virus (isolate BK)Mutation(s): 0 
Gene Names: POL
EC: 2.7.7.48
UniProt
Find proteins for P26663 (Hepatitis C virus genotype 1b (isolate BK))
Explore P26663 
Go to UniProtKB:  P26663
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26663
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
T18
Query on T18

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
N-{3-[6-fluoro-1-(4-fluorobenzyl)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,4-benzothiazin-7-yl}methanesulfonamide
C25 H19 F2 N3 O6 S2
SNCZSOMZWKLZNB-UHFFFAOYSA-N
NI
Query on NI

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
NICKEL (II) ION
Ni
VEQPNABPJHWNSG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
T18 Binding MOAD:  3G86 IC50: 5 (nM) from 1 assay(s)
PDBBind:  3G86 IC50: 5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.192 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.915α = 90
b = 106.169β = 90
c = 126.94γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description