3CTH

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a aminopyridine based inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

Cai, Z.-W.Wei, D.Schroeder, G.M.Cornelius, L.A.Kim, K.Chen, X.-T.Schmidt, R.J.Williams, D.K.Tokarski, J.S.An, Y.Sack, J.S.Manne, V.Kamath, A.Zhang, Y.Marathe, P.Hunt, J.T.Lombardo, L.J.Fargnoli, J.Borzilleri, R.M.

(2008) Bioorg Med Chem Lett 18: 3224-3229

  • DOI: https://doi.org/10.1016/j.bmcl.2008.04.047
  • Primary Citation of Related Structures:  
    3CTH, 3CTJ

  • PubMed Abstract: 

    A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. zhenwei.cai@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
319
Query on 319

Download Ideal Coordinates CCD File 
B [auth A]N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide
C20 H16 F2 N4 O3
USBSTVPJNQLYEM-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
319 PDBBind:  3CTH IC50: 110 (nM) from 1 assay(s)
BindingDB:  3CTH IC50: 35 (nM) from 1 assay(s)
Binding MOAD:  3CTH IC50: 35 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.212 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.752α = 90
b = 47.637β = 90
c = 152.471γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-06-10 
  • Deposition Author(s): Sack, J.

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection