2OF4

crystal structure of furanopyrimidine 1 bound to lck


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.264 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: Synthesis, SAR, and pharmacokinetic properties.

Martin, M.W.Newcomb, J.Nunes, J.J.Bemis, J.E.McGowan, D.C.White, R.D.Buchanan, J.L.Dimauro, E.F.Boucher, C.Faust, T.Hsieh, F.Huang, X.Lee, J.H.Schneider, S.Turci, S.M.Zhu, X.

(2007) Bioorg Med Chem Lett 17: 2299-2304

  • DOI: https://doi.org/10.1016/j.bmcl.2007.01.048
  • Primary Citation of Related Structures:  
    2OF2, 2OF4

  • PubMed Abstract: 

    2,3-Diarylfuro[2,3-b]pyridine-4-amines are a novel class of potent and selective inhibitors of Lck. The discovery, synthesis, and structure activity relationships of this series of inhibitors are reported. The most promising compounds were also profiled to deduce their pharmacokinetic properties.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. matmarti@amgen.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase LCK271Homo sapiensMutation(s): 0 
Gene Names: LCK
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P06239 (Homo sapiens)
Explore P06239 
Go to UniProtKB:  P06239
PHAROS:  P06239
GTEx:  ENSG00000182866 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06239
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
979
Query on 979

Download Ideal Coordinates CCD File 
B [auth A]5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE
C24 H25 N5 O
PTILEOLOGGMFCS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
979 PDBBind:  2OF4 IC50: 81 (nM) from 1 assay(s)
BindingDB:  2OF4 IC50: 81 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.264 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.1α = 90
b = 73.6β = 90
c = 91.9γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2007-02-27 
  • Deposition Author(s): Martin, M.W.

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-27
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Refinement description