Histone Deacetylase Inhibitors: New Promise in the Treatment of Immune and Inflammatory Diseases

Stephen      J. Shuttleworth; Sarah      G. Bailey; Paul      A. Townsend

Abstract

The development of Histone Deacetylase (HDAC) inhibitors has, until recently, principally been driven by their potential as anti-cancer agents. However, there is emerging evidence that HDAC inhibitors could have utility in the treatment of chronic immune and inflammatory disorders, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, airway hyperresponsiveness and organ transplant rejection. Here we discuss the merits of various, structurally-distinct HDAC inhibitors as potential anti-inflammatory therapeutics and provide examples of the novel medicinal chemistry approaches being undertaken to realize HDAC as a druggable target in this clinical setting.

Keywords: Histone deacetylases, inhibitors, inflammation, immune disease, FK228, deacetylases, multiple sclerosis, rheumatoid arthritis, psoriasis, histones, nuclear proteins, T-cell lymphoma, (FDA), GM-CSF, TNFα, TGFβ, (MMPs), iNOS, IL-1β, IFN-, (Tregs), Cyclosporin-A, IL-2, (ZEB), (CtBP), CD4+ T, FR276457, (GVHD), (T-cell depletion), phosphorylation, (IBD), (SLE), CD28, RASFs, KBH-A42, Trichostatin-A, Vorinostat, chemokines, CTCL