Histone Demethylases (HDMs)

Histones constitute the basic scaffold proteins around which DNA is wound to form nucleosomes which are packed into higher order structures to form chromatin. Methylated lysine and arginine residues on histone tails are believed to be regulatory hallmarks for discriminating transcriptionally active and inactive chromatin. Demethylases are enzymes that remove methyl (-CH3) groups from target proteins. Histone demethylases (HDMs) are particularly responsible for removal of methyl groups predominantly from Arginine and Lysine residues in Histone proteins. There are two main types of HDMs based on their functional mechanism: a flavin adenine dinucleotide (FAD)-dependent amine oxidase, and a Fe (II) and α-ketoglutarate-dependent dioxygenase.

Several families (Lysine Demethylase 1-6 also called KDM 1-6) of histone demethylases exist categorized on the basis of their substrates and functional domains. Different HDMs play different roles in cellular function. In fact, an elaborate "histone code" has been developed to indicate the substrate for a histone demethylase. The first histone demethylase to be discovered was lysine-specific demethylase 1 (LSD1), but further research has identified a family of histone demethylases; the Jumonji C domain-containing demethylases (JMJD). The pattern of methylation on a particular segment of DNA offers an exquisitely sophisticated and dynamic regulatory mechanism for epigenetic control of gene expression. HDMs have critical roles in creating suitable methylation patterns for tumor cells to gain metastatic potential. Thus the tremendous therapeutic potential of modulating genetically aberrant or overexpressed HDMs across a wide range of human diseases is increasingly becoming evident. In fact, robust high-throughput screening and hit-finding approaches have enabled the development of highly specific and potent inhibitors.
BioVision offers several HDM inhibitors as part of its catalog. These encompass all areas of biological and oncological research.

Histone Demethylase (HDM) Inhibitors Subcategories