3I81

Crystal structure of insulin-like growth factor 1 receptor (IGF-1R-WT) complex with BMS-754807 [1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoro-3-pyridinyl)-2-methyl-L-prolinamide]


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.08 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.221 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development.

Wittman, M.D.Carboni, J.M.Yang, Z.Lee, F.Y.Antman, M.Attar, R.Balimane, P.Chang, C.Chen, C.Discenza, L.Frennesson, D.Gottardis, M.M.Greer, A.Hurlburt, W.Johnson, W.Langley, D.R.Li, A.Li, J.Liu, P.Mastalerz, H.Mathur, A.Menard, K.Patel, K.Sack, J.Sang, X.Saulnier, M.Smith, D.Stefanski, K.Trainor, G.Velaparthi, U.Zhang, G.Zimmermann, K.Vyas, D.M.

(2009) J Med Chem 52: 7360-7363

  • DOI: https://doi.org/10.1021/jm900786r
  • Primary Citation of Related Structures:  
    3I81

  • PubMed Abstract: 

    This report describes the biological activity, characterization, and SAR leading to 9d (BMS-754807) a small molecule IGF-1R kinase inhibitor in clinical development.


  • Organizational Affiliation

    Bristol-Myers Squibb Co, Wallingford, Connecticut 06492, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin-like growth factor 1 receptor315Homo sapiensMutation(s): 0 
Gene Names: IGF1R
EC: 2.7.1.112
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EBI
Query on EBI

Download Ideal Coordinates CCD File 
B [auth A]1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl}-N-(6-fluoropyridin-3-yl)-2-methyl-L-proli namide
C23 H24 F N9 O
LQVXSNNAFNGRAH-QHCPKHFHSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
EBI PDBBind:  3I81 IC50: 13 (nM) from 1 assay(s)
BindingDB:  3I81 IC50: 2 (nM) from 1 assay(s)
Binding MOAD:  3I81 IC50: 13 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.08 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.221 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.366α = 90
b = 41.097β = 120.57
c = 78.816γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling
BUSTERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2009-12-22 
  • Deposition Author(s): Sack, J.S.

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations, Structure summary