title: Recent progress in the discovery of epigenetic inhibitors for the treatment of cancer.
abstract: Epigenetics investigates heritable changes in gene transcription that do not involve a change in DNA sequence, and an increased understanding in the role of epigenetic misregulation as a key contributor to cancer has triggered the development of epigenetic targeted cancer therapies. Among these include efforts around a class of enzymes known as histone methyltransferases (HMTs). The level of interest in the development of HMT inhibitors as a class of anticancer agents has significantly grown beyond academic settings, and in the last 5 years whole research groups from biotech and big pharma have been dedicated to this area. There are now multiple reports describing small-molecule HMT inhibitors, including chemical probes and drug candidates entering the clinic as first-in-class agents. Recent progress in this emerging area is the topic of this chapter.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, Inc., 1250 South Collegeville Road, Collegeville, PA, 19426, USA, sharad.k.verma@gsk.com.
authors.forename: Sharad K
authors.initials: SK
authors.lastname: Verma
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000187:drug effects*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors
chemical_list: C473477:DOT1L protein, human; D008780:Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2