4JI9

JAK2 kinase (JH1 domain) in complex with TG101209

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

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Ligand Structure Quality Assessment 


This is version 1.2 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 JAK2
A, B
300Homo 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
1M3
Query on 1M3
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		N-tert-butyl-3-[(5-methyl-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide
C26 H35 N7 O2 S
JVDOKQYTTYUYDV-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
1M3 BindingDB:  4JI9 IC50: min: 1.4, max: 97.6 (nM) from 5 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.992α = 90
b = 111.992β = 90
c = 70.467γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata 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: 2024-11-27
    Changes: Data collection, Database references, Derived calculations, Structure summary