The future therapeutic potential of histone demethylases: A critical analysis.
Once regarded as an irreversible modification, the methylation of histone protein tails has recently been highlighted following the identification of enzymes capable of histone demethylation in response to developmental or environmental cues. An awareness of the dynamic nature of histone modification has stimulated interest in the concept that drugs targeting histone methylation/demethylation might provide treatments for cancer, inflammation and metabolic disorders. However, epigenetic therapies that target histone demethylation are at the concept stage. Histone demethylases and their potential as therapeutic targets are discussed in this review.
Natoli
Gioacchino
G
European Institue of Oncology, Department of Experimental Oncology, Milan, Italy. gioacchino.natoli@ifom-ieo-campus.it
Testa
Giuseppe
G
De Santa
Francesca
F
D000818:Animals; D003640:Dealkylation; D015195:Drug Design; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008239:Lysine; D008745:Methylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D055550:Protein Stability; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; D006657:Histones; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine