Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists

Hong      Shen; Carl      G. Maki

doi:10.2174/138161211795222603

Abstract

Restoring p53 activity by inhibiting the interaction between p53 and MDM2 represents an attractive approach for cancer therapy. To this end, a number of small-molecule p53-MDM2 binding inhibitors have been developed during the past several years. Nutlin-3 is a potent and selective small-molecule MDM2 antagonist that has shown considerable promise in pre-clinical studies. This review will highlight recent advances in the development of small-molecule MDM2 antagonists as potential cancer therapeutics, with special emphasis on Nutlin-3.

Keywords: Nutlin-3, p53, MDM2, therapy, antagonist, apoptosis, MDMX, p14/ARF, NUTLIN, doxorubicin, therapeutic, choriocarcinoma, Molecular Mechanisms, Antitumor, Perifosine