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Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors
Author(s) -
Milite Ciro,
Feoli Alessandra,
Viviano Monica,
Rescigno Donatella,
Mai Antonello,
Castellano Sabrina,
Sbardella Gianluca
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600272
Subject(s) - methyltransferase , histone h4 , histone methyltransferase , histone , lysine , proliferating cell nuclear antigen , biochemistry , histone h3 , dna replication , microbiology and biotechnology , chemistry , biology , cell growth , dna , methylation , amino acid
SETD8/SET8/Pr‐SET7/KMT5A is the only known lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20) in vivo. The methyltransferase activity of SETD8 has been implicated in many essential cellular processes, including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. In addition to H4K20, SETD8 monomethylates non‐histone substrates including proliferating cell nuclear antigen and p53. During the past decade, different structural classes of inhibitors targeting various lysine methyltransferases have been designed and developed. However, the development of SETD8 inhibitors is still in its infancy. This review covers the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases, and cellular activity.