4GG7

Crystal structure of cMET in complex with novel inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.27 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors.

Wu, K.Ai, J.Liu, Q.Chen, T.Zhao, A.Peng, X.Wang, Y.Ji, Y.Yao, Q.Xu, Y.Geng, M.Zhang, A.

(2012) Bioorg Med Chem Lett 22: 6368-6372

  • DOI: https://doi.org/10.1016/j.bmcl.2012.08.075
  • Primary Citation of Related Structures:  
    4GG5, 4GG7

  • PubMed Abstract: 

    Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgw-atinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a-c possessing an O-linkage were inactive, whilst the N-linked analogues 15a-c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC(50) value of 6.5 nM. Further structural modifications based on this compound were undergoing.


  • Organizational Affiliation

    Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hepatocyte growth factor receptor319Homo sapiensMutation(s): 0 
Gene Names: CMETMET
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
0J8
Query on 0J8

Download Ideal Coordinates CCD File 
B [auth A]N-(3-nitrobenzyl)-6-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)pyrido[2,3-d]pyrimidin-4-amine
C23 H21 F3 N8 O2
OIYLUARXJZNDPY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0J8 PDBBind:  4GG7 Ki: 6.3 (nM) from 1 assay(s)
Binding MOAD:  4GG7 IC50: 6.5 (nM) from 1 assay(s)
BindingDB:  4GG7 IC50: 6.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.27 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.210 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.867α = 90
b = 65.867β = 90
c = 187.176γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-03
    Type: Initial release
  • Version 1.1: 2012-10-17
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations