3NW7

Crystal structure of insulin-like growth factor 1 receptor (IGF-1R-WT) complex with a carbon-linked proline isostere inhibitor (34)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 

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Literature

Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase.

Sampognaro, A.J., Wittman, M.D., Carboni, J.M., Chang, C., Greer, A.F., Hurlburt, W.W., Sack, J.S., Vyas, D.M.

(2010) Bioorg Med Chem Lett 20: 5027-5030

  • DOI: https://doi.org/10.1016/j.bmcl.2010.07.045
  • Primary Citation of Related Structures:  
    3NW5, 3NW6, 3NW7

  • PubMed Abstract: 

    Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as isosteric proline replacements in a series of insulin-like growth factor I receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in potency to proline-containing reference compounds were shown to project a key fluoropyridine amide into a common space, while less potent compounds were not able to do so for reasons of stereochemistry or structural rigidity.

    • Organizational Affiliation: 

    Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA. anthony.sampognaro@bms.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin-like growth factor 1 receptor307Homo sapiensMutation(s): 0 
Gene Names: IGF1R
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08069 (Homo sapiens)
Explore P08069 
Go to UniProtKB:  P08069
PHAROS:  P08069
GTEx:  ENSG00000140443 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08069
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LGV
Query on LGV
Download Ideal Coordinates CCD File 
B [auth A]N-({4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl}methyl)-6-fluoropyridine-3-carboxamide
C19 H17 F N8 O
FQECDJFBKXFTIW-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LGV BindingDB:  3NW7 IC50: min: 5.3, max: 40 (nM) from 2 assay(s)
PDBBind:  3NW7 IC50: 5.3 (nM) from 1 assay(s)
Binding MOAD:  3NW7 IC50: 5.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.165 
  • R-Value Observed: 0.168 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.508α = 90
b = 41.123β = 121.64
c = 80.385γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2010-07-28 
    • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations