Zinc-dependent Deacetylase (HDAC) Inhibitors with Different Zinc Binding Groups.

Abstract

The state of histone acetylation plays a very crucial role in carcinogenesis and its development by chromatin remodeling and thus altering transcription of oncogenes and tumor suppressor genes. Such epigenetic regulation was controlled by zinc-dependent histone deacetylases (HDACs), one of the major regulators. Due to the therapeutic potential of HDACs as one of the promising drug targets in cancer, HDAC inhibitors have been intensively investigated over the last few decades. Notably, there are five HDAC inhibitors already approved to the market. Vorinostat (SAHA), Belinostat (PXD-101) and Romidepsin (FK228) have been approved by Food and Drug Administration (FDA) in USA for treating cutaneous T-cell lymphoma (CTCL) or peripheral T cell lymphoma (PTCL) while Panbinostat (LBH-589) has also been approved by the FDA for the treatment of multiple myeloma. Recently, Chidamide was approved by China Food and Drug Administration (CFDA) for the treatment of PTCL. The structural feature of almost all HDAC inhibitors consists of Cap group, linker, and zinc-binding group (ZBG). The binding of ZBG groups to zinc ion plays a decisive role in the inhibition of HDAC. Therefore, we will summarize the developed HDAC inhibitors according to different ZBG groups and discuss their binding mode with zinc ion.