Histone deacetylases inhibitors: Conjugation to other anti-tumour pharmacophores provides novel tools for cancer treatment

摘要

Histone deacetylases (HDACs) are involved in the removal of acetyl groups from intracellular proteins. The catalytic activity of HDACs plays a major role in numerous biological processes, including cell-cycle regulation, cell proliferation and apoptosis. Importantly, tumour development and progression have been associated with altered expression and mutations of genes that encode members of the HDAC family. This family comprises at least 18 enzymes that are responsible for the post-translational deacetylation of several histone and non-histone proteins. HDACs hold a place among the most promising therapeutic targets for the treatment of cancer and there are growing efforts to optimise HDAC inhibition therapy. The authors believe that there is the need for an innovative pharmacological strategy, if the field wants to significantly ameliorate the current shortcomings of the current cancer therapies, in particular, perhaps a strategy that focuses on developing single HDAC inhibitor-based compounds, which can modulate the functions of additional intracellular oncogenic targets via conjugation to other anti-tumour pharmacophores.