Chemical Biology of Lysine Demethylases
Tom D Heightman*, #
Identifiers and Pagination:Year: 2011
Issue: Suppl 1
First Page: 62
Last Page: 71
Publisher Id: CCGTM-5-62
Article History:Received Date: 27/1/2011
Revision Received Date: 12/4/2011
Acceptance Date: 25/4/2011
Electronic publication date: 22/8/2011
Collection year: 2011
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Abnormal levels of DNA methylation and/or histone modifications are observed in patients with a wide variety of chronic diseases. Methylation of lysines within histone tails is a key modification that contributes to increased gene expression or repression depending on the specific residue and degree of methylation, which is in turn controlled by the interplay of lysine methyl transferases and demethylases. Drugs that target these and other enzymes controlling chromatin modifications can modulate the expression of clusters of genes, potentially offering higher therapeutic efficacy than classical agents acting on downstream biochemical pathways that are susceptible to degeneracy. Lysine demethylases, first discovered in 2004, are the subject of increasing interest as therapeutic targets. This review provides an overview of recent findings implicating lysine demethylases in a range of therapeutic areas including oncology, immunoinflammation, metabolic disorders, neuroscience, virology and regenerative medicine, together with a summary of recent advances in structural biology and small molecule inhibitor discovery, supporting the tractability of the protein family for the development of selective druglike inhibitors.