3KSQ

Discovery of C-Imidazole Azaheptapyridine FPT Inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.193 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Discovery of C-imidazole azaheptapyridine FPT inhibitors.

Zhu, H.Y.Cooper, A.B.Desai, J.Njoroge, G.Kirschmeier, P.Bishop, W.R.Strickland, C.Hruza, A.Doll, R.J.Girijavallabhan, V.M.

(2010) Bioorg Med Chem Lett 20: 1134-1136

  • DOI: https://doi.org/10.1016/j.bmcl.2009.12.013
  • Primary Citation of Related Structures:  
    3KSQ

  • PubMed Abstract: 

    The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is described. This novel class of compounds are sub nM FPT enzyme inhibitors with potent cellular inhibitory activities. This series also has reduced hERG activity versus previous N-linked imidazole series. X-ray of compound 10a bound to FTase revealed strong interaction between bridgehead imidazole 3N with catalytic zinc atom.


  • Organizational Affiliation

    Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. hugh.zhu@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Farnesyltransferase, CAAX box, alpha377Rattus norvegicusMutation(s): 0 
Gene Names: Fnta
EC: 2.5.1.58
UniProt
Find proteins for Q04631 (Rattus norvegicus)
Explore Q04631 
Go to UniProtKB:  Q04631
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04631
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein farnesyltransferase subunit beta437Rattus norvegicusMutation(s): 0 
Gene Names: Fntb
EC: 2.5.1.58
UniProt
Find proteins for Q02293 (Rattus norvegicus)
Explore Q02293 
Go to UniProtKB:  Q02293
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02293
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Z96
Query on Z96

Download Ideal Coordinates CCD File 
F [auth B]tert-butyl 4-{(11S)-8-chloro-6-[(R)-hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl}piperazine-1-carboxylate
C28 H32 Cl N5 O3
YZFYPECRJZGSGJ-IZZNHLLZSA-N
FPP
Query on FPP

Download Ideal Coordinates CCD File 
E [auth B]FARNESYL DIPHOSPHATE
C15 H28 O7 P2
VWFJDQUYCIWHTN-YFVJMOTDSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth B]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth B]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FPP BindingDB:  3KSQ Kd: 2 (nM) from 1 assay(s)
Z96 BindingDB:  3KSQ IC50: 0.3 (nM) from 1 assay(s)
PDBBind:  3KSQ IC50: 0.38 (nM) from 1 assay(s)
Binding MOAD:  3KSQ IC50: 0.38 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.193 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 171.122α = 90
b = 171.122β = 90
c = 69.269γ = 120
Software Package:
Software NamePurpose
StructureStudiodata collection
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling
BUSTERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description