Discovery of highly potent p53-MDM2 antagonists and structural basis for anti-acute myeloid leukemia activities.

ABSTRACT: The inhibition of p53-MDM2 interaction is a promising new approach to non-genotoxic cancer treatment. A potential application for drugs blocking the p53-MDM2 interaction is acute myeloid leukemia (AML) due to the occurrence of wild type p53 (wt p53) in the majority of patients. Although there are very promising preclinical results of several p53-MDM2 antagonists in early development, none of the compounds have yet proven the utility as a next generation anticancer agent. Herein we report the design, synthesis and optimization of YH239-EE (ethyl ester of the free carboxylic acid compound YH239), a potent p53-MDM2 antagonizing and apoptosis-inducing agent characterized by a number of leukemia cell lines as well as patient-derived AML blast samples. The structural basis of the interaction bet

SUBMITTER: Huang Y 

PROVIDER: S-EPMC3985958 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature