Recent development of selective inhibitors targeting the HDAC6 as anti-cancer drugs: Structure, function and design

HDAC6, a member of the histone deacetylase family, mainly is a cytosolic protein and regulates cell growth by acting on non-histone substrates, such as alpha-tubulin, cortactin, heat shock protein HSP90, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), that are closely related to the proliferation, invasion, immune escape and angiogenesis of cancer tissues. The approved drugs targeting the HDACs are all pan-inhibitors and have many side effects due to their lack of selectivity. Therefore, development of selective inhibitors of HDAC6 has attracted much attention in the field of cancer therapy. In this review, we will summarize the relationship between HDAC6 and cancer, and discuss the design strategies of HDAC6 inhibitors for cancer treatment in recent years.

Automated summary

HDAC6 is a cytosolic protein belonging to the histone deacetylase family, which regulates cell growth by acting on non-histone substrates closely related to cancer tissues. The lack of selectivity in approved HDAC inhibitors has led to many side effects, thus the development of selective HDAC6 inhibitors has gained significant attention in cancer therapy. This review summarizes the relationship between HDAC6 and cancer, and discusses the design strategies of HDAC6 inhibitors for cancer treatment in recent years.