3ETA

Kinase domain of insulin receptor complexed with a pyrrolo pyridine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase.

Patnaik, S.Stevens, K.L.Gerding, R.Deanda, F.Shotwell, J.B.Tang, J.Hamajima, T.Nakamura, H.Leesnitzer, M.A.Hassell, A.M.Shewchuck, L.M.Kumar, R.Lei, H.Chamberlain, S.D.

(2009) Bioorg Med Chem Lett 19: 3136-3140

  • DOI: https://doi.org/10.1016/j.bmcl.2008.12.110
  • Primary Citation of Related Structures:  
    3ETA

  • PubMed Abstract: 

    Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays.


  • Organizational Affiliation

    GlaxoSmithKline, Oncology R&D, NC 27709, USA. patnaiks@mail.nih.gov


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
insulin receptor, kinase domain
A, B
317Homo sapiensMutation(s): 0 
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
351
Query on 351

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
1-(3-{5-[4-(aminomethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}phenyl)-3-(2-phenoxyphenyl)urea
C33 H27 N5 O2
KSTUYVHCHCYOAB-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
351 PDBBind:  3ETA IC50: 14 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.105α = 90
b = 94.751β = 90
c = 129.858γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CNSrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-05-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Refinement description