Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development.
J Med Chem
; 56(14): 5979-83, 2013 Jul 25.
Article
in En
| MEDLINE
| ID: mdl-23808545
ABSTRACT
Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.
Full text:
1
Database:
MEDLINE
Main subject:
Pyrrolidines
/
Tumor Suppressor Protein p53
/
Proto-Oncogene Proteins c-mdm2
/
Para-Aminobenzoates
/
Antineoplastic Agents
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2013
Type:
Article
Affiliation country:
United States