3CD8

X-ray Structure of c-Met with triazolopyridazine Inhibitor.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.236 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery and Optimization of Triazolopyridazines as Potent and Selective Inhibitors of the c-Met Kinase.

Albrecht, B.K.Harmange, J.C.Bauer, D.Berry, L.Bode, C.Boezio, A.A.Chen, A.Choquette, D.Dussault, I.Fridrich, C.Hirai, S.Hoffman, D.Larrow, J.F.Kaplan-Lefko, P.Lin, J.Lohman, J.Long, A.M.Moriguchi, J.O'Connor, A.Potashman, M.H.Reese, M.Rex, K.Siegmund, A.Shah, K.Shimanovich, R.Springer, S.K.Teffera, Y.Yang, Y.Zhang, Y.Bellon, S.F.

(2008) J Med Chem 51: 2879-2882

  • DOI: https://doi.org/10.1021/jm800043g
  • Primary Citation of Related Structures:  
    3CCN, 3CD8

  • PubMed Abstract: 

    Tumorigenesis is a multistep process in which oncogenes play a key role in tumor formation, growth, and maintenance. MET was discovered as an oncogene that is activated by its ligand, hepatocyte growth factor. Deregulated signaling in the c-Met pathway has been observed in multiple tumor types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.


  • Organizational Affiliation

    Amgen Inc., Cambridge, MA 02139, USA. brian.albrecht@amgen.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hepatocyte growth factor receptor310Homo sapiensMutation(s): 1 
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
L5G
Query on L5G

Download Ideal Coordinates CCD File 
B [auth A]7-methoxy-4-[(6-phenyl[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy]quinoline
C22 H17 N5 O2
HEAIZQNMNCHNFD-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
L5G PDBBind:  3CD8 IC50: 9 (nM) from 1 assay(s)
BindingDB:  3CD8 IC50: min: 9, max: 90 (nM) from 5 assay(s)
Binding MOAD:  3CD8 IC50: 9 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.236 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.008α = 90
b = 43.208β = 90
c = 158.219γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description