The search for new histone deacetylase (HDAC) inhibitors, particularly isoform-selective ones, is gaining traction in drug discovery, especially following the approval of romidepsin for cancer treatment.
A new method utilizing ultra-high-performance liquid chromatography - mass spectrometry (UHPLC-MS) measures the inhibitory activity of compounds on HDAC1 and HDAC6 in live HeLa cells, reflecting natural cell conditions better than traditional assays.
This method's adaptability to various cell lines and its ability to quantify synthetic substrates make it promising for identifying selective HDAC compounds, as demonstrated through tests with trichostatin A, MS275, and tubastatin A on HeLa cells.