Description
Tenovin-
1 is a small molecule activator of p53 transcriptional activity. At 10 μM, it elevates p53 expression in MCF-
7 cells within two hours of treatment and longer-
term exposure significantly decreases the growth of BL2 Burkitt’s lymphoma and ARN8 melanoma cells. Functioning upstream of p53, tenovin-
1 acts by inhibiting the deacetylase activity of purified human SIRT1 and SIRT2, members of NAD
+-
dependent class III histone deacetylases that belong to the sirtuin family. While tenovin-
1 demonstrates low genotoxicity, the compound has poor water solubility, which limits its uses
in vivo.
Uses
Tenovin 1 is a sirtuin inhibitor.
Definition
ChEBI: N-[(4-acetamidoanilino)-sulfanylidenemethyl]-4-tert-butylbenzamide is a member of thioureas.
Biological Activity
p53 activator that protects against MDM2-mediated p53 degradation. Elevates levels of p53 and p21 CIP/WAF1 and induces expression from an endogenous p53-dependent promoter. Exhibits potent antiproliferative activity in vitro .
References
Lain et al. (2008), Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator; Cancer Cell, 13 454
Sonnemann et al. (2014), p53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors; Br. J. Cancer 110 656
Nihal et al. (2014), SIRT1 is upregulated in cutaneous T-cell lymphoma, and its inhibition induces growth arrest and apoptosis; Cell Cycle 13 632
Wilking et al. (2014), SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation; Arch. Biochem. Biophys. 563 94
Marx et al. (2018), The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing’s sarcoma cell line; New Drugs 36 396
Bang et al. (2019), Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes; Biomol. Ther. (Seoul) 27 283
