Discovery of a novel, highly potent, and selective THIENO[3,2- D]PYRIMIDINONE-based CDC7 inhibitor with a quinuclidine moiety (tak- 931) as an orally active investigational anti-tumor agent

Structure

x-ray diffraction · 4 distinct chains · 40% helix, 13% strand (DSSP).

Ligands and binding sites

• O1V · 2-[(2S)-1-azabicyclo[2.2.2]octan-2-yl]-6-(5-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one · ligand · 4 copies · chains A, B, C, D

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

Pockets

18 pockets found on a 1 Å grid, 9 with a druggability of 0.5 or more.

Interfaces

6 interfaces between chains.

• A–D · 1906 Ų buried · 18 hydrogen bonds · protein-protein
• B–C · 1702 Ų buried · 16 hydrogen bonds · protein-protein
• A–B · 879 Ų buried · 9 hydrogen bonds · protein-protein
• C–D · 877 Ų buried · 8 hydrogen bonds · protein-protein
• B–D · 266 Ų buried · 2 hydrogen bonds · protein-protein

Compared structures

• 6P5P · Discovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidi -Based Cdc7… · the same entry in another collection · chain D against D, TM-score 1.00
• O75116 · AlphaFold monomer V2.0 prediction for rho-associated protein kinase 2 (O75116) · a predicted model of the same protein · chain D against A, TM-score 0.99

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 O75116
• Elsewhere: RCSB PDB 6P5P · PDBe 6P5P · UniProt O75116