Tenovin-1

Tenovin-1, a p53 activator, protects p53 from MDM2-mediated degradation. Tenovin-1 acts through inhibition of the protein-deacetylating activities of SirT1 and SirT2. Tenovin-1 is also a dihydroorotate dehydrogenase (DHODH) inhibitor^[1][2]. IC50 & Target: Sirtuin, MDM-2/p53^[1] In Vitro: Tenovin-1 protects p53 from mdm2-mediated degradation with little effect on p53 synthesis. Tenovin-1 targets a factor(s) upstream of p53 that not only modulates p53 function but also other cellular pathways. Tenovin-1 (10 μM) inhibits SirT2 deacetylase activity^[1].
Tenovin-1 (1-10 μM) induces a bell-shaped concentration-dependent cell death in SK-N-MC cells. Tenovin-1 alters the gene and protein expression of Bcl-2 family members. However, Tenovin-1 has a more powerful effect both on mRNA and protein expression levels at a lower concentration than does the higher concentration. Furthermore, Tenovin-1-induced cytotoxic effects depend on caspases in p53 wild-type WE-68 cells, but not in p53 null SK-N-MC cells. AIF plays a major role in tenovin-1-induced cell death in p53 null SK-N-MC cells, but not in p53 wild-type WE-68 cells. Reactive oxygen species are also involved in tenovin-1-mediated cell death in SK-N-MC cells. In addition, Tenovin-1 causes DNA damage in SK-N-MC cells^[3]. Tenovin-1 (5 μM) increases the nuclear size in glioblastoma cells and rat primary astrocytes. Tenovin-1 induces cellular senescence, wich does not appear to be related to cell death^[4].
Tenovin-1 (10 μM) reduces proliferation and anchorage independent growth of NSCLC cells. Tenovin-1 also inhibits cell growth of H358 lung cancer cells^[5]. In Vivo: Tenovin-1 (92 mg/kg, i.p.) reduces growth of tumors in SCID mice derived from BL2 cells or ARN8 cells^[5].