3L8V

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor C-MET in complex with a biarylamine based inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.185 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.

Williams, D.K.Chen, X.T.Tarby, C.Kaltenbach, R.Cai, Z.W.Tokarski, J.S.An, Y.Sack, J.S.Wautlet, B.Gullo-Brown, J.Henley, B.J.Jeyaseelan, R.Kellar, K.Manne, V.Trainor, G.L.Lombardo, L.J.Fargnoli, J.Borzilleri, R.M.

(2010) Bioorg Med Chem Lett 20: 2998-3002

  • DOI: https://doi.org/10.1016/j.bmcl.2010.01.042
  • Primary Citation of Related Structures:  
    3L8V

  • PubMed Abstract: 

    Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. david.williams@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hepatocyte growth factor receptor314Homo sapiensMutation(s): 3 
Gene Names: MET
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08581 (Homo sapiens)
Explore P08581 
Go to UniProtKB:  P08581
PHAROS:  P08581
GTEx:  ENSG00000105976 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08581
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
L8V
Query on L8V

Download Ideal Coordinates CCD File 
B [auth A]2-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}amino)-N-(2,4-difluorophenyl)pyridine-3-carboxamide
C23 H16 F3 N5 O2
VPOULRXFJKYXDN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
L8V BindingDB:  3L8V IC50: 8 (nM) from 1 assay(s)
Binding MOAD:  3L8V IC50: 8 (nM) from 1 assay(s)
PDBBind:  3L8V IC50: 8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.8α = 90
b = 47.25β = 90
c = 154.5γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-05-05 
  • Deposition Author(s): Sack, J.

Revision History  (Full details and data files)

  • Version 1.0: 2010-05-05
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2018-03-14
    Changes: Structure summary
  • Version 1.3: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-09-06
    Changes: Data collection, Refinement description