Piperazinones

Nutlins are a family of small molecule, cis-imidazoline analogs, which inhibit the interaction between MDM2 and tumor suppressor p53, stabilizing p53 and triggering cell death and senescence. Three nutlins were discovered in the initial small molecule screen (nutlin-1, nutlin-2, and nutlin-3), but nutlin-3 is most commonly used in anti-cancer studies. Nutlins disrupt the p53–MDM2 interaction by occupying a p53-binding pocket of MDM2. Many tumors that express normal p53 and normal or elevated levels of MDM2 may be targeted using nutlin. Nutlin-3 acts quickly in vitro, leading to increased level