› 4zyf

X-ray diffraction
1.8Å resolution

Discovery of NVP-CGM097 - a highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumors: Hdm2 (MDM2) complexed with NVP-CGM097

Released:
DOI: 10.2210/pdb4zyf/pdb
PDB entry 4zyf coloured by chain, front view.
PDB entry 4zyf coloured by chain, side view.
PDB entry 4zyf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors.
Holzer P, Masuya K, Furet P, Kallen J, Valat-Stachyra T, Ferretti S, Berghausen J, Bouisset-Leonard M, Buschmann N, Pissot-Soldermann C, Rynn C, Ruetz S, Stutz S, Chène P, Jeay S, Gessier F
J Med Chem 58 6348-58 (2015)
PMID: 26181851

Function and Biology Details

Reaction catalysed: 
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine
Biochemical function:
  • not assigned
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-169499 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
E3 ubiquitin-protein ligase Mdm2 Chain: A
Molecule details ›
Chain: A
Length: 96 amino acids
Theoretical weight: 11.16 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q00987 (Residues: 17-111; Coverage: 19%)
Gene name: MDM2
Sequence domains: SWIB/MDM2 domain
Structure domains: SWIB/MDM2 domain

Ligands and Environments

2 bound ligands:
Ligand 4T4 1 x 4T4
Ligand CL 1 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P6122
Unit cell:
a: 55.609Å b: 55.609Å c: 108.28Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.227 0.227 0.232
Expression system: Escherichia coli

Quick links

Citations

36 review citations

Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.
Lu et al. (2020)
35 more

10 mentions without citation

Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives.
Fang et al. (2020)
9 more