4JIA

JAK2 kinase (JH1 domain) in complex with compound 9

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history. 


Literature

2-Amino-[1,2,4]triazolo[1,5-a]pyridines as JAK2 inhibitors.

Siu, M., Pastor, R., Liu, W., Barrett, K., Berry, M., Blair, W.S., Chang, C., Chen, J.Z., Eigenbrot, C., Ghilardi, N., Gibbons, P., He, H., Hurley, C.A., Kenny, J.R., Cyrus Khojasteh, S., Le, H., Lee, L., Lyssikatos, J.P., Magnuson, S., Pulk, R., Tsui, V., Ultsch, M., Xiao, Y., Zhu, B.Y., Sampath, D.

(2013) Bioorg Med Chem Lett 23: 5014-5021

  • DOI: https://doi.org/10.1016/j.bmcl.2013.06.008
  • Primary Citation of Related Structures:  
    4JI9, 4JIA

  • PubMed Abstract: 

    The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed.

    • Organizational Affiliation: 

    Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, United States. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2300Homo 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1K3
Query on 1K3
Download Ideal Coordinates CCD File 
B [auth A]5-(4-methoxyphenyl)-N-[4-(4-methylpiperazin-1-yl)phenyl][1,2,4]triazolo[1,5-a]pyridin-2-amine
C24 H26 N6 O
DPVQBIWIVWTDRV-UHFFFAOYSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-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
1K3 PDBBind:  4JIA Ki: 0.6 (nM) from 1 assay(s)
BindingDB:  4JIA Ki: 0.6 (nM) from 1 assay(s)
IC50: 22 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.172 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.42α = 90
b = 70.2β = 98.95
c = 50.54γ = 90
Software Package:
Software NamePurpose
BOSdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-08-07
    Type: Initial release
  • Version 1.1: 2013-08-21
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2023-12-06
    Changes: Data collection
  • Version 1.4: 2024-11-20
    Changes: Structure summary