Increasing knowledge of the relationship between p53 and MDM2 has led to development of potential small molecule inhibitorsuseful for clinical studies. Herein, we discuss the patented (2006-2010) inhibitors of p53-MDM2 interaction. The anticancer agentsdiscussed in this review belong to several different chemical classes including benzodiazepinediones, cis-imidazolines, oxindoles, spirooxindoles,and numerous miscellaneous groups. This review also provides comprehensive information on inhibitors of p53-MDM2 interactionthat are currently being tested in clinical trials. It is important to note that many of the disclosed inhibitors need further validationto be considered as bona fide inhibitors of p53-MDM2 interaction and some will not be further considered for future studies. On the otherhand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in earlyphases of trials in cancer patients. AT-219, a spiroindolinone in late stage preclinical studies is a likely candidate to proceed into clinicaltrials. It remains to be seen how these inhibitors will perform in future clinical studies as single agents and in combination with the currentlyapproved chemotherapeutic agents.
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|Titolo:||Small-Molecule Inhibitors of p53-MDM2 Interaction: the 2006-2010 Update|
|Data di pubblicazione:||2011|
|Appare nelle tipologie:||1.1 Articolo in rivista|