3B2W

Crystal structure of pyrimidine amide 11 bound to Lck

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.230 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history. 


Literature

N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.

Deak, H.L., Newcomb, J.R., Nunes, J.J., Boucher, C., Cheng, A.C., DiMauro, E.F., Epstein, L.F., Gallant, P., Hodous, B.L., Huang, X., Lee, J.H., Patel, V.F., Schneider, S., Turci, S.M., Zhu, X.

(2008) Bioorg Med Chem Lett 18: 1172-1176

  • DOI: https://doi.org/10.1016/j.bmcl.2007.11.123
  • Primary Citation of Related Structures:  
    3B2W

  • PubMed Abstract: 

    N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.

    • Organizational Affiliation: 

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


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase LCK277Homo 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
9NH
Query on 9NH
Download Ideal Coordinates CCD File 
B [auth A]N-[5-({[2-fluoro-3-(trifluoromethyl)phenyl]amino}carbonyl)-2-methylphenyl]-4-methoxy-2-[(4-piperazin-1-ylphenyl)amino]pyrimidine-5-carboxamide
C31 H29 F4 N7 O3
RZSXAGWVTKQZAS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
9NH Binding MOAD:  3B2W IC50: 0.6 (nM) from 1 assay(s)
PDBBind:  3B2W IC50: 0.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.308 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.230 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.18α = 90
b = 75.19β = 112.35
c = 47.11γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2007-12-18 
    • Deposition Author(s): Huang, X.

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description