4JU6

Crystal structure of hcv ns5b polymerase in complex with compound 24


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.237 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay.

Stammers, T.A.Coulombe, R.Duplessis, M.Fazal, G.Gagnon, A.Garneau, M.Goulet, S.Jakalian, A.Laplante, S.Rancourt, J.Thavonekham, B.Wernic, D.Kukolj, G.Beaulieu, P.L.

(2013) Bioorg Med Chem Lett 23: 6879-6885

  • DOI: https://doi.org/10.1016/j.bmcl.2013.09.102
  • Primary Citation of Related Structures:  
    4JU3, 4JU4, 4JU6, 4JU7

  • PubMed Abstract: 

    Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar.


  • Organizational Affiliation

    Medicinal Chemistry Department, Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 Cunard Street, Laval, Quebec H7S 2G5, Canada. Electronic address: timothy.stammers@boehringer-ingelheim.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Genome polyprotein
A, B
576Hepatitis C virus isolate HC-J4Mutation(s): 0 
Gene Names: NS5B
EC: 3.4.22 (PDB Primary Data), 3.4.21.98 (PDB Primary Data), 3.6.1.15 (PDB Primary Data), 3.6.4.13 (PDB Primary Data), 2.7.7.48 (PDB Primary Data)
UniProt
Find proteins for O92972 (Hepatitis C virus genotype 1b (strain HC-J4))
Explore O92972 
Go to UniProtKB:  O92972
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO92972
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1O6
Query on 1O6

Download Ideal Coordinates CCD File 
C [auth A]2-{[(trans-4-methylcyclohexyl)carbonyl](propan-2-yl)amino}-5-phenoxybenzoic acid
C24 H29 N O4
ICLINNCKFPTXOX-IYARVYRRSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
D [auth A],
E [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1O6 PDBBind:  4JU6 IC50: 670 (nM) from 1 assay(s)
Binding MOAD:  4JU6 IC50: 670 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.237 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 106.84α = 90
b = 108.07β = 90
c = 135.33γ = 90
Software Package:
Software NamePurpose
APEXdata collection
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2013-11-27 
  • Deposition Author(s): Coulombe, R.

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-27
    Type: Initial release
  • Version 1.1: 2013-12-18
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description