4ZIM

CRYSTAL STRUCTURE OF JANUS KINASE 2 IN COMPLEX WITH A 9H-CARBAZOLE-1-CARBOXAMIDE INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors.

Zimmermann, K.Sang, X.Mastalerz, H.A.Johnson, W.L.Zhang, G.Liu, Q.Batt, D.Lombardo, L.J.Vyas, D.Trainor, G.L.Tokarski, J.S.Lorenzi, M.V.You, D.Gottardis, M.M.Lippy, J.Khan, J.Sack, J.S.Purandare, A.V.

(2015) Bioorg Med Chem Lett 25: 2809-2812

  • DOI: https://doi.org/10.1016/j.bmcl.2015.04.101
  • Primary Citation of Related Structures:  
    4ZIM

  • PubMed Abstract: 

    The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.


  • Organizational Affiliation

    Bristol-Myers Squibb Co., 5 Research Parkway, Wallingford, CT 06492-1951, USA. Electronic address: Kurt.Zimmermann@bms.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2
A, B
321Homo 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
4OK
Query on 4OK

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
3-(3,4-dichlorophenyl)-6-(morpholin-4-ylcarbonyl)-9H-carbazole-1-carboxamide
C24 H19 Cl2 N3 O3
FYEWVKCORNQLFP-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
4OK BindingDB:  4ZIM IC50: min: 2.4, max: 200 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.65 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.39α = 90
b = 112.39β = 90
c = 70.81γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2015-06-03 
  • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-03
    Type: Initial release
  • Version 1.1: 2015-06-17
    Changes: Database references
  • Version 1.2: 2016-07-20
    Changes: Data collection
  • Version 1.3: 2017-11-22
    Changes: Derived calculations, Refinement description