3Q32

Structure of Janus kinase 2 with a pyrrolotriazine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.178 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Pyrrolo[1,2-f]triazines as JAK2 inhibitors: Achieving potency and selectivity for JAK2 over JAK3.

Harikrishnan, L.S.Kamau, M.G.Wan, H.Inghrim, J.A.Zimmermann, K.Sang, X.Mastalerz, H.A.Johnson, W.L.Zhang, G.Lombardo, L.J.Poss, M.A.Trainor, G.L.Tokarski, J.S.Lorenzi, M.V.You, D.Gottardis, M.M.Baldwin, K.F.Lippy, J.Nirschl, D.S.Qiu, R.Miller, A.V.Khan, J.Sack, J.S.Purandare, A.V.

(2011) Bioorg Med Chem Lett 21: 1425-1428

  • DOI: https://doi.org/10.1016/j.bmcl.2011.01.022
  • Primary Citation of Related Structures:  
    3Q32

  • PubMed Abstract: 

    SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed.


  • Organizational Affiliation

    Bristol-Myers Squibb Co., Princeton, NJ 08543-4000, USA. lalgudi.harikrishnan@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2
A, B
301Homo 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
J2I
Query on J2I

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2-(2,6-difluoro-4-methoxyphenyl)-1-(4-{4-[(3-methyl-1H-pyrazol-5-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl}piperazin-1-yl)ethanone
C23 H24 F2 N8 O2
CFXACTJFCDMPJK-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
J2I Binding MOAD:  3Q32 IC50: 1.8 (nM) from 1 assay(s)
BindingDB:  3Q32 IC50: 1.8 (nM) from 1 assay(s)
PDBBind:  3Q32 IC50: 1.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.178 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.59α = 90
b = 110.59β = 90
c = 69.96γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
AUTOBUSTERrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-02-16 
  • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance