1VJY

Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Identification of 1,5-Naphthyridine Derivatives as a Novel Series of Potent and Selective TGF-beta Type I Receptor Inhibitors.

Gellibert, F.Woolven, J.Fouchet, M.-H.Mathews, N.Goodland, H.Lovegrove, V.Laroze, A.Nguyen, V.-L.Sautet, S.Wang, R.Janson, C.Smith, W.Krysa, G.Boullay, V.De Gouville, A.-C.Huet, S.Hartley, D.

(2004) J Med Chem 47: 4494-4506

  • DOI: https://doi.org/10.1021/jm0400247
  • Primary Citation of Related Structures:  
    1VJY

  • PubMed Abstract: 

    Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.


  • Organizational Affiliation

    Department of Medicinal Chemistry, GlaxoSmithKline, 25-27 Avenue du Québec, 91951 Les Ulis, France. fjg23217@gsk.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TGF-beta receptor type I303Homo sapiensMutation(s): 0 
EC: 2.7.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for P36897 (Homo sapiens)
Explore P36897 
Go to UniProtKB:  P36897
PHAROS:  P36897
GTEx:  ENSG00000106799 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP36897
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
460
Query on 460

Download Ideal Coordinates CCD File 
B [auth A]2-[5-(6-METHYLPYRIDIN-2-YL)-2,3-DIHYDRO-1H-PYRAZOL-4-YL]-1,5-NAPHTHYRIDINE
C17 H15 N5
YRBHUKMLAGQYHS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
460 Binding MOAD:  1VJY IC50: 23 (nM) from 1 assay(s)
PDBBind:  1VJY IC50: 23 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.223 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.069α = 90
b = 75.775β = 90
c = 89.589γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
CNXrefinement
HKL-2000data reduction
CNXphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2004-08-31
    Type: Initial release
  • Version 1.1: 2008-04-26
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations