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 .
in vivo
Tenovin-1 (92 mg/kg, i.p.) reduces growth of tumors in SCID mice derived from BL2 cells or ARN8 cells[5].
IC 50
MDM-2/p53; DHODH; Sirtuin
References
[1] SONIA LAIN. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator.[J]. Cancer Cell, 2008, 13 5: 454-463. DOI:
10.1016/j.ccr.2008.03.004[2] J SONNEMANN. p53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors[J]. British Journal of Cancer, 2013, 110 3: 656-667. DOI:
10.1038/bjc.2013.742[3] MINAKSHI NIHAL Gary S W Nihal Ahmad. SIRT1 is upregulated in cutaneous T-cell lymphoma, and its inhibition induces growth arrest and apoptosis.[J]. Cell Cycle, 2014, 13 4: 632-640. DOI:
10.4161/cc.27523[4] MELISSA J. WILKING . SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation[J]. Archives of biochemistry and biophysics, 2014, 563: Pages 94-100. DOI:
10.1016/j.abb.2014.04.001[5] CHRISTIAN MARX. 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.[J]. Investigational New Drugs, 2018: 396-406. DOI:
10.1007/s10637-017-0541-1[6] MINJI BANG. Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes.[J]. Biomolecules & Therapeutics, 2019, 27 3: 283-289. DOI:
10.4062/biomolther.2018.107
