Isoform-Selective HDAC Inhibitor Therapy for Transplantation (original) (raw)

The 18 known mammalian histone/protein deacetylases (HDACs) are divided into 4 groups, termed class I (HDAC1, HDAC2, HDAC3, HDAC8), class IIa (HDAC4, HDAC5, HDAC7, HDAC9), class IIb (HDAC6, HDAC10), class III (SIRT1-7) and class IV (HDAC11) enzymes 1. While these enzymes were initially defined by their ability to deacetylate histones and dampen histone-DNA and histone-protein interactions, they are now recognized as regulating the functions of thousands of nonhistone proteins 2. A large number of broadly active pharmacologic HDAC inhibitors (pan-HDACi) have been developed and are in clinical trials as anti-cancer agents due to their abilities to promote tumor cell-cycle arrest, differentiation and apoptosis 3. There is also interest in the potential use of HDACi therapy for autoimmunity and transplantation, but there are concerns that the various pan-HDACi compounds may be too broadly acting and/or toxic for clinical use beyond oncology.