N-[[[4-(Acetylamino)phenyl]amino]thioxomethyl]-4-(1,1-dimethylethyl)-benzamide (Tenovin 1)
• p53 activator that protects against MDM2-mediated p53 degradation. Elevates levels of p53 and p21CIP/WAF1 and induces expression from an endogenous p53-dependent promoter. Exhibits potent antiproliferative activity in vitro
OTAVAchemicals Catalogue Number: 7215270035
CAS Registry Number: 380315-80-0
Purity: 95%+ (HPLC)
Ref.: Lain et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell (2008), 13, 454-463
Abstract: We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biological tools for the study of sirtuin function as well as their potential therapeutic interest.