3E62

Fragment based discovery of JAK-2 inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Fragment-based discovery of JAK-2 inhibitors.

Antonysamy, S.Hirst, G.Park, F.Sprengeler, P.Stappenbeck, F.Steensma, R.Wilson, M.Wong, M.

(2009) Bioorg Med Chem Lett 19: 279-282

  • DOI: https://doi.org/10.1016/j.bmcl.2008.08.064
  • Primary Citation of Related Structures:  
    3E62, 3E63, 3E64

  • PubMed Abstract: 

    Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.


  • Organizational Affiliation

    Medicinal Chemistry, SGX Pharmaceuticals, Inc, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2293Homo sapiensMutation(s): 0 
Gene Names: JAK2
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for O60674 (Homo sapiens)
Explore O60674 
Go to UniProtKB:  O60674
PHAROS:  O60674
GTEx:  ENSG00000096968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60674
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5B1
Query on 5B1

Download Ideal Coordinates CCD File 
B [auth A]5-bromo-1H-indazol-3-amine
C7 H6 Br N3
OMPYFDJVSAMSMA-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
5B1 BindingDB:  3E62 IC50: 4.09e+4 (nM) from 1 assay(s)
Binding MOAD:  3E62 IC50: 4.09e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.92 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.169 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.302α = 90
b = 102.297β = 90
c = 68.386γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-02-01
    Changes: Structure summary
  • Version 1.3: 2012-02-08
    Changes: Structure summary