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Through the use of the ICF and the necessity ofdeveloping clinical models to address function and outcomes in multiple settings, the impor-tance of this framework was veri?ed.

In this chapter, we review the approaches for screening anddiscovering efcient and selective MDM2 inhibitors with emphasis on the mostadvanced synthetic small molecules that interfere with the p53-MDM2 interac-tion and are currently on Phase I clinical trials.

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