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Biological Activity:

NSC319726 is a potent and selective activator of mutant p53^R175 (EC₅₀ ~8 nM in mutant p53 cell lines but with >100-fold selectivity in wild type cells). It has potent growth inhibitory activity in mutant p53 cells, particularly for the p53^R175 mutant. Mechanistic studies revealed that NSC319726 restores WT structure and function to the p53^R175 mutant. It kills p53^R175H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele-specific mutant p53-dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. NSC319726 is an attractive lead compound for anti-cancer drug development.

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How to Use:

• In vitro:? NSC319726 was used at 1 μM in vitro and in cellular assays.
• In vivo: NSC319726 was administrated by intraperitoneal injection (IP) to mice at 5-10 mg/kg once per day for up to 7 days.

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Reference:

1. 1. Yu X, et al. Allele-specific p53 mutant reactivation. (2012) Cancer Cell. 21(5):614-25.
2. 2. Charlotte Harrison. Anticancer drugs: Reactivating p53. (2012) Nature Reviews Drug Discovery 11, 517.