4TWC

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

PDB DOI: https://doi.org/10.2210/pdb4TWC/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2014-06-30 Released: 2014-10-08
Deposition Author(s): Bischof, J., Leban, L., Zaja, M., Grothey, A., Radunsky, B., Othersen, O., Strobl, S., Vitt, D., Knippschild, U.

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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wwPDB Validation 3D Report Full Report

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

PubMed: 22331384 Search on PubMedSearch on PubMed Central
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.

Macromolecule Content

Total Structure Weight: 71.36 kDa
Atom Count: 5,908
Modelled Residue Count: 585
Deposited Residue Count: 590
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Casein kinase I isoform delta	A, B	295	Homo sapiens	Mutation(s): 1 Gene Names: CSNK1D, HCKID 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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P48730
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
37J Query on 37J Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain R [auth B] MOL2 format, chain I [auth A] MOL2 format, chain R [auth B] mmCIF format, chain I [auth A] mmCIF format, chain R [auth B]	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		Interactions Focus chain I [auth A] Focus chain R [auth B] Interactions & Density Focus chain I [auth A] Focus chain R [auth B]
BOG Query on BOG Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain J [auth A] MOL2 format, chain H [auth A] MOL2 format, chain J [auth A] mmCIF format, chain H [auth A] mmCIF format, chain J [auth A]	H [auth A], J [auth A]	octyl beta-D-glucopyranoside C₁₄ H₂₈ O₆ HEGSGKPQLMEBJL-RKQHYHRCSA-N		Interactions Focus chain H [auth A] Focus chain J [auth A] Interactions & Density Focus chain H [auth A] Focus chain J [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain F [auth A] SDF format, chain E [auth A] SDF format, chain K [auth B] SDF format, chain L [auth B] SDF format, chain M [auth B] SDF format, chain N [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain F [auth A] MOL2 format, chain E [auth A] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain F [auth A] mmCIF format, chain E [auth A] mmCIF format, chain K [auth B] mmCIF format, chain L [auth B] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B]	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		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain K [auth B] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain K [auth B] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain O [auth B] SDF format, chain P [auth B] MOL2 format, chain G [auth A] MOL2 format, chain O [auth B] MOL2 format, chain P [auth B] mmCIF format, chain G [auth A] mmCIF format, chain O [auth B] mmCIF format, chain P [auth B]	G [auth A], O [auth B], P [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain O [auth B] Focus chain P [auth B] Interactions & Density Focus chain G [auth A] Focus chain O [auth B] Focus chain P [auth B]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain Q [auth B] MOL2 format, chain Q [auth B] mmCIF format, chain Q [auth B]	Q [auth B]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain Q [auth B] Interactions & Density Focus chain Q [auth B]

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 = 52.04	α = 90
b = 134.721	β = 99.68
c = 56.845	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
ADSC	data collection
SCALA	data scaling
PDB_EXTRACT	data extraction
MOSFLM	data reduction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-10-08

Deposition Author(s):

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

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4TWC

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

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

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)