Histone Methyltransferase Inhibitors: Novel Epigenetic Agents for Cancer Treatment
C. Zagni, U. Chiacchio and A. Rescifina
Pages 167-185 (19)
Epigenetics is defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence. The
gene transcription is strictly correlated to chromatin structure, which could undergo covalent modifications of histones involving acetylation,
methylation, phosphorylation and ubiquitination. Alterations in histones are implicated in many diseases, including cancer, by leading
to tumor suppressor silencing or pro-apoptotic proteins downregulation. Although post-translational addition of methyl groups to the
histone lysine has been discovered three decades ago, the importance of this epigenetic modification has emerged only in the last few
years. Thenceforward histone methyltransferase inhibitors have been developed as potential therapeutic cancer agents. It should not be
long before some selective inhibitors make their way into clinical trials. This review is mainly focused on the evolution in the development
of new epigenetic modifier molecules modulating histone marks.
HMT inhibitors, HKMT inhibitors, HRMT inhibitors, histone methylation, drug discovery, S-adenosyl-L-methionine (SAM), Sadenosyl-L-homocysteine (SAH), DNA-methylation, chromatin, epigenetic
Dipartimento di Scienze del Farmaco, Universita di Catania, Viale Andrea Doria 6, 95125 Catania, Italy.