Discovery of checkpoint kinase inhibitor AZD7762 by structure based design and optimization of thiophene carboxamide ureas

Structure

x-ray diffraction · 2 distinct chains · 34% helix, 22% strand (DSSP).

Ligands and binding sites

• YDJ · 5-(3-fluorophenyl)-N-[(3S)-3-piperidyl]-3-ureido-thiophene-2-carboxamide · ligand · 2 copies · chains A, B
• PO4 · Phosphate ion · ion · 2 copies · chains A, B

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

3 pockets found on a 1 Å grid, 3 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 327 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 modified (oxidation).

Compared structures

• 2YDJ · Discovery of Checkpoint Kinase Inhibitor AZD7762 by Structure Based Design and… · the same entry in another collection · chain A against A, TM-score 1.00
• 2C3K · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.99
• O14757 · AlphaFold monomer V2.0 prediction for SERINE/THREONINE-protein kinase CHK1 (O14757) · a predicted model of the same protein · chain B against A, TM-score 0.99
• 2C3L · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.99
• 2C3J · Identification of a buried pocket for potent and selective inhibition of CHK1: prediction… · a predicted model of the same protein · chain A against A, TM-score 0.98

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt O14757
• Elsewhere: RCSB PDB 2YDJ · PDBe 2YDJ · UniProt O14757