[HTML][HTML] A novel sirtuin 2 (SIRT2) inhibitor with p53-dependent pro-apoptotic activity in non-small cell lung cancer
G Hoffmann, F Breitenbücher, M Schuler… - Journal of Biological …, 2014 - ASBMB
Sirtuin 2 (SIRT2) is an NAD+-dependent protein deacetylase whose targets include histone
H4 lysine 16, p53, and α-tubulin. Because deacetylation of p53 regulates its effect on
apoptosis, pharmacological inhibition of SIRT2-dependent p53 deacetylation is of great
therapeutic interest for the treatment of cancer. Here, we have identified two structurally
related compounds, AEM1 and AEM2, which are selective inhibitors of SIRT2 (IC 50 values
of 18.5 and 3.8 μm, respectively), but show only weak effects on other sirtuins such as …
H4 lysine 16, p53, and α-tubulin. Because deacetylation of p53 regulates its effect on
apoptosis, pharmacological inhibition of SIRT2-dependent p53 deacetylation is of great
therapeutic interest for the treatment of cancer. Here, we have identified two structurally
related compounds, AEM1 and AEM2, which are selective inhibitors of SIRT2 (IC 50 values
of 18.5 and 3.8 μm, respectively), but show only weak effects on other sirtuins such as …