4TWC

2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4- carboxamide derivatives as potent inhibitors of CK1d/e


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1d/e.

Bischof, J.Leban, J.Zaja, M.Grothey, A.Radunsky, B.Othersen, O.Strobl, S.Vitt, D.Knippschild, U.

(2012) Amino Acids 43: 1577-1591

  • DOI: https://doi.org/10.1007/s00726-012-1234-x
  • Primary Citation of Related Structures:  
    4TWC

  • PubMed Abstract: 

    In this study we identified two heterocyclic compounds (5 and 6) as potent and specific inhibitors of CK1δ (IC(50) = 0.040 and 0.042 μM, respectively). Whereas compound 5 exhibited fivefold higher affinity towards CK1δ than to CK1ε (IC(50) CK1ε = 0.199 μM), compound 6 also inhibited CK1ε (IC(50) = 0.0326 μM) in the same range as CK1δ. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1δ. X-ray analysis of 5 bound to CK1δ demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biological approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, our optimizations lead to the development of new highly selective CK1δ and ε specific inhibitors with biological activity.


  • Organizational Affiliation

    Department of General, Visceral and Transplantation Surgery, Surgery Centre, University of Ulm, Steinhövel Str. 9, 89075, Ulm, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase I isoform delta
A, B
295Homo sapiensMutation(s): 1 
Gene Names: CSNK1DHCKID
EC: 2.7.11.1 (PDB Primary Data), 2.7.11.26 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P48730 (Homo sapiens)
Explore P48730 
Go to UniProtKB:  P48730
PHAROS:  P48730
GTEx:  ENSG00000141551 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48730
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
37J
Query on 37J

Download Ideal Coordinates CCD File 
I [auth A],
R [auth B]
2-{[2-(trifluoromethoxy)benzoyl]amino}-N-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide
C20 H11 F6 N5 O3 S
GUWQZSKMUJFZMM-UHFFFAOYSA-N
BOG
Query on BOG

Download Ideal Coordinates CCD File 
H [auth A],
J [auth A]
octyl beta-D-glucopyranoside
C14 H28 O6
HEGSGKPQLMEBJL-RKQHYHRCSA-N
SO4
Query on SO4

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C [auth A]
D [auth A]
E [auth A]
F [auth A]
K [auth B]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

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G [auth A],
O [auth B],
P [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
Q [auth B]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.04α = 90
b = 134.721β = 99.68
c = 56.845γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
ADSCdata collection
SCALAdata scaling
PDB_EXTRACTdata extraction
MOSFLMdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-08
    Type: Initial release
  • Version 1.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary