Exploring Epigenetic Drugs in the Regulation of Inflammatory Autoimmune Diseases

Abstract

During recent years, numerous studies have shown that epigenetics, heritable changes that do not involve alterations in the DNA sequence, play an important role in the development, function, and regulation of the immune system as well as in the onset and progress of autoimmune diseases. For that reason, in the following chapter, we will review some of the most important concepts about epigenetics and how they modulate the development and function of immune cells, specifically macrophages, dendritic cells, and T cells. Moreover, we will review the role of epigenetics on autoimmune diseases, as well as the use of pharmacological modulation of the epigenetic machinery, as an innovative way to approach a potential new treatment or improve the current treatments of autoimmune diseases.

Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer

“…Over the last several years, lysine demethylase (KDM) enzymes have gained recognition as targets for drug-mediated therapy against various diseases and ailments ranging from cancer, inflammation, and viral infection. − Originally, and within a clinical context of prostate cancer (PCa), the flavin adenosine dinucleotide (FAD)-dependent KDM1 demethylase was demonstrated to directly interact with nuclear-localized androgen receptor (AR), stimulating gene transcription by removing repressive mono- and di-methyl epigenetic marks at lysine 9 of histone H3. Subsequent reports expanded upon histone demethylation activities by demonstrating that isoforms of the KDM4 subfamily (KDM4A, KDM4B, KDM4C, and KDM4D) also interact with the nuclear-localized AR − and stimulate gene transcription by removing repressive di- and tri-methyl epigenetic marks at lysine 9 of histone H3 (the latter of which is denoted here as H3K9me3).…”

“…Since these discoveries, several additional KDMs have been identified, whose collective activities are now recognized as important mediators of disease progression. Accordingly, many KDMs are current targets of small-molecule discovery campaigns with hopes that inhibitors found therein may prove to be of therapeutic value. − …”