A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53^wt osteosarcoma cells.

ABSTRACT: The p53 protein is engaged in the repair of DNA mutations and elimination of heavily damaged cells, providing anticancer protection. Dysregulation of p53 activity is a crucial step in carcinogenesis. This dysregulation is often caused by the overexpression of negative regulators of p53, among which MDM2 is the most prominent one. Antagonizing MDM2 with small molecules restores the activity of p53 in p53 wild-type (p53^wt ) cells and thus provides positive outcomes in the treatment of p53^wt cancers. Previously, we have reported the discovery of a panel of fluoro-substituted indole-based antagonists of MDM2. Here, we demonstrate the biological activity and stereoselectivity of the most active compound from this series. Both enantiomers of the esterified form of the compo

SUBMITTER: Skalniak L 

PROVIDER: S-EPMC6634946 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature