Advances in histone deacetylase 8 selective inhibitors

Histone deacetylase 8(HDAC8)is a zinc-dependent class I histone deacetylase, closely related to human pathophysiology. HDAC8 involves in various critical signaling networks and is implicated as a therapeutic target in various diseases, including cancer, X-linked intellectual disability and parasitic infections. More and more selective HDAC8 inhibitors have been developed based on deepening study of its well-characterized crystal structure. They are mainly divided into several categories such as phenyl hydroxamic acids, indoles, ortho-aryl-N-hydroxycinnamides, azetidinones etc. . Current challenges remain in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors. Herein, we reviewed the progress in the study of structure and functions of HDAC8 as well as the development of selective HDAC8 inhibitors.