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 2I1R

Novel Thiazolones as HCV NS5B Polymerase Inhibitors: Further Designs, Synthesis, SAR and X-ray Complex Structure

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

Novel thiazolones as HCV NS5B polymerase allosteric inhibitors: Further designs, SAR, and X-ray complex structure.

Yan, S., Larson, G., Wu, J.Z., Appleby, T., Ding, Y., Hamatake, R., Hong, Z., Yao, N.

(2007) Bioorg Med Chem Lett 17: 63-67

  • DOI: https://doi.org/10.1016/j.bmcl.2006.09.095
  • Primary Citation of Related Structures:  
    2I1R

  • PubMed Abstract: 

    Structure-activity relationships (SAR) of 1 against HCV NS5B polymerase were described. SAR explorations and further structure-based design led to the identifications of 2 and 3 as novel HCV NS5B inhibitors. X-ray structure of 3 in complex with NS5B polymerase was obtained at a resolution of 2.2A, and confirmed the design.

    • Organizational Affiliation: 

    Valeant Pharmaceuticals Research and Development, 3300 Hyland Ave., Costa Mesa, CA 92626, USA. syan@valeant.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase (NS5B) (P68)
A, B
576Hepacivirus hominisMutation(s): 0 
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 AnnotationsExpand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VXR
Query on VXR
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		(5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-2-{[(S)-(4-FLUOROPHENYL)(1H-TETRAZOL-5-YL)METHYL]AMINO}-1,3-THIAZOL-4(5H)-ONE
C18 H15 F N6 O2 S
BKZOQCGDCHOGOQ-MZLJFPOFSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
VXR PDBBind:  2I1R IC50: 9700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.602α = 90
b = 106.117β = 90
c = 126.605γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-31
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations