Mouse double minute 2 protein (MDM2) is an E3 ubiquitin-protein ligase that binds and ubiquitinates the tumor suppressor p53, leading to its degradation by the proteasome. SP 141 is a cell-permeable inhibitor of MDM2 (Ki = 28 nM). Binding of MDM2 by SP 141 promotes its auto-ubiquitination and proteasomal degradation. SP 141 induces cell cycle arrest and apoptosis in breast and pancreatic cancer cell lines and inhibits xenograft tumor growth in vivo. This compound has a short half-life in plasma and wide tissue distribution in tumor-bearing nude mice.
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