2WOT

ALK5 IN COMPLEX WITH 4-((5,6-dimethyl-2-(2-pyridyl)-3-pyridyl)oxy)-N-(3,4,5-trimethoxyphenyl)pyridin-2-amine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Rapid Generation of a High Quality Lead for Transforming Growth Factor-Beta (Tgf-Beta) Type I Receptor (Alk5).

Goldberg, F.W.Ward, R.A.Powell, S.J.Debreczeni, J.E.Norman, R.A.Roberts, N.J.Dishington, A.P.Gingell, H.J.Wickson, K.F.Roberts, A.L.

(2009) J Med Chem 52: 7901

  • DOI: https://doi.org/10.1021/jm900807w
  • Primary Citation of Related Structures:  
    2WOT, 2WOU

  • PubMed Abstract: 

    A novel class of 4-pyridinoxy-2-anilinopyridine-based TGF-beta type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors is reported. The binding mode of this scaffold was successfully predicted by analyzing possible docked binding modes of literature inhibitors and novel synthetic ideas. Compounds such as 19 are potent ALK5 inhibitors with good physicochemical and pharmacokinetic properties and thus represent high quality leads for further optimization.


  • Organizational Affiliation

    AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TGF-BETA RECEPTOR TYPE-1306Homo sapiensMutation(s): 0 
EC: 2.7.11.30
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZZG
Query on ZZG

Download Ideal Coordinates CCD File 
B [auth A]4-[(5,6-DIMETHYL-2,2'-BIPYRIDIN-3-YL)OXY]-N-(3,4,5-TRIMETHOXYPHENYL)PYRIDIN-2-AMINE
C26 H26 N4 O4
RNLQQRFAMDEKKT-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ZZG BindingDB:  2WOT IC50: 44 (nM) from 1 assay(s)
EC50: 55 (nM) from 1 assay(s)
Binding MOAD:  2WOT IC50: 44 (nM) from 1 assay(s)
PDBBind:  2WOT IC50: 44 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.933α = 90
b = 78.218β = 90
c = 89.074γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2011-11-23
    Changes: Database references, Structure summary
  • Version 1.3: 2014-11-19
    Changes: Data collection
  • Version 1.4: 2018-04-04
    Changes: Data collection
  • Version 1.5: 2019-05-08
    Changes: Data collection, Experimental preparation