2QHN

Crystal Structure of Chek1 in Complex with Inhibitor 1a


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors.

Brnardic, E.J.Garbaccio, R.M.Fraley, M.E.Tasber, E.S.Steen, J.T.Arrington, K.L.Dudkin, V.Y.Hartman, G.D.Stirdivant, S.M.Drakas, B.A.Rickert, K.Walsh, E.S.Hamilton, K.Buser, C.A.Hardwick, J.Tao, W.Beck, S.C.Mao, X.Lobell, R.B.Sepp-Lorenzino, L.Yan, Y.Ikuta, M.Munshi, S.K.Kuo, L.C.Kreatsoulas, C.

(2007) Bioorg Med Chem Lett 17: 5989-5994

  • DOI: https://doi.org/10.1016/j.bmcl.2007.07.051
  • Primary Citation of Related Structures:  
    2QHM, 2QHN

  • PubMed Abstract: 

    The development of 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones as inhibitors of Chk1 kinase is described. Introduction of a fused ring at the C7/C8 positions of the pyrazoloquinolinone provided an increase in potency while guidance from overlapping inhibitor bound Chk1 X-ray crystal structures contributed to the discovery of a potent and solubilizing propyl amine moiety in compound 52 (Chk1 IC(50)=3.1 nM).


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. edward_brnardic@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase Chk1323Homo sapiensMutation(s): 0 
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O14757 (Homo sapiens)
Explore O14757 
Go to UniProtKB:  O14757
PHAROS:  O14757
GTEx:  ENSG00000149554 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14757
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
582
Query on 582

Download Ideal Coordinates CCD File 
B [auth A]5-ETHYL-3-METHYL-1,5-DIHYDRO-4H-PYRAZOLO[4,3-C]QUINOLIN-4-ONE
C13 H13 N3 O
ASEHARDUZDZEKS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
582 Binding MOAD:  2QHN IC50: 980 (nM) from 1 assay(s)
PDBBind:  2QHN IC50: 980 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.14α = 90
b = 65.68β = 94.55
c = 58.23γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description