UF 010 is a novel and selective class I HDAC inhibitor with IC50 values of 0.5, 0.1, 0.06, 1.5, 9.1, 15.3 and 44.5 μM for HDAC1, 2, 3, 8, 6, 10 and 11 [1].
Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from ε-N-acetyl lysines on histones, allowing the histones to wrap the DNA more tightly. DNA expression is regulated by de-acetylation and acetylation.
UF 010 is a novel and selective class I HDAC inhibitor, and is a fast-on but slow-off inhibitor. In fluorescence assays, UF 010 (5 nM to 100 μM) exhibited inhibitory potency with IC50 values of 0.5, 0.1, 0.06, 1.5, 9.1, 15.3 and 44.5 μM for HDAC1, 2, 3, 8, 6, 10 and 11, and exhibited IC50 values of >100 μM for HDAC4, 5, 7 and 9. In HCT116 cells, UF 010 induced the accumulation of acetylated histones at all sites examined and significantly inhibited cellular HDACs. In HCT116 cell cultures, UF 010 inhibited HDAC with IC50 value of 1.8 μM. UF 010 also exhibited IC50 value of 11.2 μM for killing cells. In HepG2 liver cancer cell line, UF 010 inhibited cell survival with IC50 value of 4.6 μM. In MDA-MB-231 cells, UF 010 induced G1/S arrest with increased cells in G1 phase and reduced cells in S phase in a dose-dependent way. UF010 at 1 μM also significantly slowed migration [1].
Reference:
[1]. Wang Y, Stowe RL, Pinello CE, et al. Identification of histone deacetylase inhibitors with benzoylhydrazide scaffold that selectively inhibit class I histone deacetylases. Chem Biol, 2015, 22(2): 273-284.