› 4ajw

X-ray diffraction
2.8Å resolution

Discovery and Optimization of New Benzimidazole- and Benzoxazole-Pyrimidone Selective PI3KBeta Inhibitors for the Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient Cancers

Released:
DOI: 10.2210/pdb4ajw/pdb
PDB entry 4ajw coloured by chain, front view.
PDB entry 4ajw coloured by chain, side view.
PDB entry 4ajw coloured by chain, top view.
Source organism: Mus musculus
Primary publication:
Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers.
Certal V, Halley F, Virone-Oddos A, Delorme C, Karlsson A, Rak A, Thompson F, Filoche-Rommé B, El-Ahmad Y, Carry JC, Abecassis PY, Lejeune P, Vincent L, Bonnevaux H, Nicolas JP, Bertrand T, Marquette JP, Michot N, Benard T, Below P, Vade I, Chatreaux F, Lebourg G, Pilorge F, Angouillant-Boniface O, Louboutin A, Lengauer C, Schio L
J Med Chem 55 4788-805 (2012)
PMID: 22524426

Function and Biology Details

Reactions catalysed: 
ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-128718 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Chains: A, B
Molecule details ›
Chains: A, B
Length: 934 amino acids
Theoretical weight: 107.21 KDa
Source organism: Mus musculus
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O35904 (Residues: 110-1043; Coverage: 90%)
Gene name: Pik3cd
Sequence domains:
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand VWN 2 x VWN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID29
Spacegroup: P21
Unit cell:
a: 63.4Å b: 220.47Å c: 78.26Å
α: 90° β: 113.87° γ: 90°
R-values:
R R work R free
0.252 0.252 0.277
Expression system: Spodoptera frugiperda

Quick links

Citations

6 review citations

Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment.
Brana et al. (2012)
5 more

3 mentions without citation

A novel PI3K inhibitor PIK-C98 displays potent preclinical activity against multiple myeloma.
Zhu et al. (2015)
2 more