› 2ydj

X-ray diffraction
1.85Å resolution

Discovery of Checkpoint Kinase Inhibitor AZD7762 by Structure Based Design and Optimization of Thiophene Carboxamide Ureas

Released:
DOI: 10.2210/pdb2ydj/pdb
PDB entry 2ydj coloured by chain, front view.
PDB entry 2ydj coloured by chain, side view.
PDB entry 2ydj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure-based design and optimization of thiophenecarboxamide ureas.
Oza V, Ashwell S, Almeida L, Brassil P, Breed J, Deng C, Gero T, Grondine M, Horn C, Ioannidis S, Liu D, Lyne P, Newcombe N, Pass M, Read J, Ready S, Rowsell S, Su M, Toader D, Vasbinder M, Yu D, Yu Y, Xue Y, Zabludoff S, Janetka J
J Med Chem 55 5130-42 (2012)
PMID: 22551018

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-127093 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine/threonine-protein kinase Chk1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 276 amino acids
Theoretical weight: 31.9 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O14757 (Residues: 1-276; Coverage: 58%)
Gene names: CHEK1, CHK1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand YDJ 2 x YDJ
Ligand PO4 2 x PO4
1 modified residue:
Ligand CSS 4 x CSS

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007
Spacegroup: P21
Unit cell:
a: 42.004Å b: 64.854Å c: 119.999Å
α: 90° β: 98.77° γ: 90°
R-values:
R R work R free
0.231 0.229 0.274
Expression system: Spodoptera frugiperda

Quick links

Citations

9 review citations

CHEK again: revisiting the development of CHK1 inhibitors for cancer therapy.
McNeely et al. (2014)
8 more

1 mention without citation

Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies.
Matthews et al. (2013)