title: Alternative strategies for targeting mouse double minute 2 activity with small molecules: novel patents on the horizon?
abstract: Most researchers have sought to restore the activity of p53 by identifying small molecules able to block the interaction of p53 with mouse double minute 2 (MDM2). To the same end, some scientists are pursuing the development of compounds that can inhibit the ubiquitin-ligase (E3) activity of MDM2. In this article, we provide a perspective review on what is known about MDM2 E3 inhibitors and what major questions remain to be addressed to boost this line of research. Recent studies provide the proof of concept that the inhibition of MDM2 E3 activity represents a viable strategy for rescuing p53 activity from MDM2 inhibitory functions. It is likely that settling some open issues such as the site of action of these compounds and their specificity towards E3 ligase enzymes will open in the near feature new horizons in cancer therapy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.forename: Nicola
authors.initials: N
authors.lastname: Giacchè
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.forename: Fabiola
authors.initials: F
authors.lastname: Moretti
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
mesh_terms: D000818:Animals; D006801:Humans; D010330:Patents as Topic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2