MDM2/MDMX inhibitor peptide: WO2008106507

Abstract

Background: The evidence that some human cancers show wild-type p53 and overexpressed levels of MDM2 and/or MDMX has fueled the search for new therapeutic agents that could rescue p53 from the inhibition of MDM2 and MDMX. Recent data, suggesting a distinct and complementary mode of action of MDM2 and MDMX in the regulation of the pro-apoptotic activity of p53, have raised the notion that the development of dual or combined inhibitors of the two oncogenic proteins may result in more effective antitumor strategies. Objective: The objective of the present patent concerns the disclosure by two researchers of the University of South Florida, reporting a dual MDM2/MDMX inhibitor peptide that selectively blocks neoplastic growth and induces apoptosis in tumor cells. Conclusion: Although the researchers' results provide the proof of concept of the feasibility of blocking both MDM2 and MDMX regulatory functions for the development of novel and more incisive p53-based anticancer strategies, their invention supplies medicinal chemists with a new interesting lead compound to aid the design of novel small-molecule inhibitors of the oncogenic proteins with drug-like properties.

Keywords::

• MDM2
• MDMX
• p53
• peptidomimetics