4HYH

X-RAY Crystal structure of compound 39 bound to human chk1 kinase domain

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors.

Huang, X., Cheng, C.C., Fischmann, T.O., Duca, J.S., Richards, M., Tadikonda, P.K., Reddy, P.A., Zhao, L., Arshad Siddiqui, M., Parry, D., Davis, N., Seghezzi, W., Wiswell, D., Shipps, G.W.

(2013) Bioorg Med Chem Lett 23: 2590-2594

  • DOI: https://doi.org/10.1016/j.bmcl.2013.02.108
  • Primary Citation of Related Structures:  
    4HYH, 4HYI

  • PubMed Abstract: 

    Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported.

    • Organizational Affiliation: 

    Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA. xiaohua.huang@merck.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine/threonine-protein kinase Chk1289Homo sapiensMutation(s): 0 
Gene Names: CHEK1, CHK1
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1AM
Query on 1AM
Download Ideal Coordinates CCD File 
B [auth A]2-(6-methoxy-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-(piperazin-1-yl)pyridin-3-yl]-1,3-thiazole-4-carboxamide
C22 H22 N6 O3 S
KLJVDMAOKMSBQX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1AM PDBBind:  4HYH IC50: 1 (nM) from 1 assay(s)
BindingDB:  4HYH IC50: min: 1, max: 3.7 (nM) from 2 assay(s)
EC50: 30 (nM) from 1 assay(s)
Binding MOAD:  4HYH IC50: 1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.204 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.97α = 90
b = 65.96β = 102.39
c = 54.42γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling
BUSTERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-06
    Type: Initial release
  • Version 1.1: 2013-05-01
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations