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. Author manuscript; available in PMC: 2013 Apr 1.
Published in final edited form as: Curr Pharm Des. 2011;17(6):560–568. doi: 10.2174/138161211795222603

Figure 1. Molecular Mechanisms of the actions of Nutlin-3.

Figure 1

Nutlin-3 binds to the p53 binding pocket in MDM2 and inhibits the p53/MDM2 interaction, leading to stabilization of p53 and induction of p53-dependent cell cycle arrest or apoptosis. Nutlin-3 can also inhibit cancer cell migration and invasion in a p53-dependent manner, most likely through inhibition of RhoA and Rac1 activity. In addition to p53, Nutlin-3 also blocks the interaction of MDM2 with p73, E2F1, HIF-1α, resulting in increased apoptosis (p73, E2F1) and decreased VEGF production and decreased angiogenesis (HIF-1α). Nutlin-3 is predicted to block the interaction of MDM2 and Numb.

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