Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development.
ACS Med Chem Lett
; 5(2): 124-7, 2014 Feb 13.
Article
in En
| MEDLINE
| ID: mdl-24900784
ABSTRACT
The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development.
Full text:
1
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2014
Type:
Article
Affiliation country:
United States