tenovin-6

Tenovin-6 is a small molecule sirtuin inhibitor that primarily targets SIRT1 and SIRT2. It was originally identified in a screen for compounds that activate the p53 tumor suppressor pathway in a p53-dependent manner without inducing DNA damage. By inhibiting the deacetylase activity of SIRT1 and SIRT2, tenovin-6 increases the levels of acetylated p53, thereby enhancing its transcriptional activity and promoting apoptosis in various cancer cell lines. In addition to its role in p53 activation, tenovin-6 has been shown to disrupt mitotic chromosome segregation and induce cytotoxicity in hematological malignancies such as diffuse large B-cell lymphoma (DLBCL) and chronic myeloid leukemia (CML). It is frequently used as a research tool to study sirtuin biology and has demonstrated synergistic effects when combined with other therapeutic agents, such as HSP90 inhibitors.