3FAA

Crystal structure of TGFbRI complexed with a 2-aminoimidazole inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.35 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

2-Aminoimidazoles inhibitors of TGF-beta receptor 1.

Bonafoux, D.Chuaqui, C.Boriack-Sjodin, P.A.Fitch, C.Hankins, G.Josiah, S.Black, C.Hetu, G.Ling, L.Lee, W.C.

(2009) Bioorg Med Chem Lett 19: 912-916

  • DOI: https://doi.org/10.1016/j.bmcl.2008.11.119
  • Primary Citation of Related Structures:  
    3FAA

  • PubMed Abstract: 

    The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.


  • Organizational Affiliation

    Abbot Laboratories, 381 Plantation Street, Worcester, MA 01605-2323, USA. dominique.bonafoux@abbott.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TGF-beta receptor type-1
A, B, C, D, E
342Homo sapiensMutation(s): 0 
Gene Names: TGFBR1
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
55F
Query on 55F

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B],
N [auth C],
P [auth D],
T [auth E]
N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide
C19 H15 F N6 O
TYPILNNEZPSNTI-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
I [auth A]
K [auth B]
L [auth B]
G [auth A],
H [auth A],
I [auth A],
K [auth B],
L [auth B],
M [auth B],
O [auth C],
Q [auth D],
R [auth D],
S [auth D],
U [auth E],
V [auth E],
W [auth E]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Binding Affinity Annotations 
IDSourceBinding Affinity
55F BindingDB:  3FAA Ki: 7.1 (nM) from 1 assay(s)
EC50: min: 180, max: 1.48e+4 (nM) from 2 assay(s)
PDBBind:  3FAA Ki: 7.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.35 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 174.861α = 90
b = 248.852β = 90
c = 138.628γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
CBASSdata collection
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-01-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations