3CS9

Human ABL kinase in complex with nilotinib


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl

Weisberg, E.Manley, P.W.Breitenstein, W.Brueggen, J.Cowan-Jacob, S.W.Ray, A.Huntly, B.Fabbro, D.Fendrich, G.Hall-Meyers, E.Kung, A.L.Mestan, J.Daley, G.Q.Callahan, L.Catley, L.Cavazza, C.Azam, M.Neuberg, D.Wright, R.D.Gilliland, D.G.Griffin, J.D.

(2005) Cancer Cell 7: 129-141

  • DOI: https://doi.org/10.1016/j.ccr.2005.01.007
  • Primary Citation of Related Structures:  
    3CS9

  • PubMed Abstract: 

    The Bcr-Abl tyrosine kinase oncogene causes chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We describe a novel selective inhibitor of Bcr-Abl, AMN107 (IC50 <30 nM), which is significantly more potent than imatinib, and active against a number of imatinib-resistant Bcr-Abl mutants. Crystallographic analysis of Abl-AMN107 complexes provides a structural explanation for the differential activity of AMN107 and imatinib against imatinib-resistant Bcr-Abl. Consistent with its in vitro and pharmacokinetic profile, AMN107 prolonged survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolonged survival in imatinib-resistant CML mouse models. AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL.


  • Organizational Affiliation

    Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase ABL1
A, B, C, D
277Homo sapiensMutation(s): 0 
Gene Names: ABL1ABLJTK7
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P00519 (Homo sapiens)
Explore P00519 
Go to UniProtKB:  P00519
PHAROS:  P00519
GTEx:  ENSG00000097007 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00519
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
NIL BindingDB:  3CS9 Ki: 1 (nM) from 1 assay(s)
Kd: min: 3.6, max: 1.00e+4 (nM) from 15 assay(s)
IC50: min: 0.33, max: 1000 (nM) from 18 assay(s)
Binding MOAD:  3CS9 IC50: 3.30e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.21 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.926α = 90
b = 118.088β = 90
c = 123.683γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations