MDM2/MDMX inhibitor peptide: WO2008106507.
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.


CONCLUSIONS
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.
Macchiarulo
Antonio
A
Università di Perugia, Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy.
Pellicciari
Roberto
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010330:Patents as Topic; D010455:Peptides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2