3EKN

Insulin receptor kinase complexed with an inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.

Chamberlain, S.D.Redman, A.M.Wilson, J.W.Deanda, F.Shotwell, J.B.Gerding, R.Lei, H.Yang, B.Stevens, K.L.Hassell, A.M.Shewchuk, L.M.Leesnitzer, M.A.Smith, J.L.Sabbatini, P.Atkins, C.Groy, A.Rowand, J.L.Kumar, R.Mook, R.A.Moorthy, G.Patnaik, S.

(2009) Bioorg Med Chem Lett 19: 360-364

  • DOI: https://doi.org/10.1016/j.bmcl.2008.11.077
  • Primary Citation of Related Structures:  
    3EKN, 3ELJ

  • PubMed Abstract: 

    The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.


  • Organizational Affiliation

    GlaxoSmithKline, Oncology R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin receptor307Homo sapiensMutation(s): 2 
Gene Names: INSR
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P06213 (Homo sapiens)
Explore P06213 
Go to UniProtKB:  P06213
PHAROS:  P06213
GTEx:  ENSG00000171105 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06213
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GS3
Query on GS3

Download Ideal Coordinates CCD File 
B [auth A]2-fluoro-6-{[2-({2-methoxy-4-[4-(1-methylethyl)piperazin-1-yl]phenyl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide
C27 H31 F N8 O2
HXZDICYKFAOZLE-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
GS3 Binding MOAD:  3EKN IC50: 2 (nM) from 1 assay(s)
PDBBind:  3EKN IC50: 4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.214 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.092α = 90
b = 69.522β = 90
c = 89.961γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-12-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-08-30
    Changes: Data collection, Refinement description