Targeting epigenetic enzymes for drug discovery.
Epigenetic control of gene transcription is the result of enzyme-mediated covalent modifications of promoter-region DNA sites and of histone proteins around which chromosomal DNA is wound. Many of the enzymes that mediate these epigenetic reactions are dysregulated in human diseases. Small molecule inhibitors against two classes of these enzymes have been approved for use in patients: DNA methyltransferase (DNMT) inhibitors and histone deacetylase inhibitors. Other classes of epigenetic enzymes have been demonstrated to have strong disease association and are currently being targeted for small molecule inhibition. In this article we review these enzymes and chemical biology approaches aimed at discovering small molecule inhibitors against them for therapeutic use.
Copeland
Robert A
RA
Epizyme Inc., 840 Memorial Drive, Cambridge, MA 02139, United States. rcopeland@Epizyme.com
Olhava
Edward J
EJ
Scott
Margaret Porter
MP
D004247:DNA / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006801:Humans
D004791:Enzyme Inhibitors; D004798:Enzymes; D004247:DNA